Pub Date : 2025-06-01Epub Date: 2025-04-19DOI: 10.1016/j.cytogfr.2025.04.001
Ying Li , Sheng-ya Yang , Ying-ru Zhang , Yan Wang
The nervous and immune systems are two major components that maintain body homeostasis, with their functional roles often overlapping significantly. Both systems are capable of identifying, integrating, and organizing responsive reactions to various external stimuli. The gut, referred to as the "second brain" and the largest immune organ in the body, serves as the most frequent focal site for neuroimmune interactions. Colorectal cancer (CRC), as the predominant solid tumor arising in this neuroimmune-rich microenvironment, remains understudied through the lens of neuroimmune regulatory mechanisms. This review systematically synthesizes current evidence to elucidate the neuroimmune axis in CRC pathogenesis, with particular emphasis on neuroimmune crosstalk-mediated remodeling of tumor immunity. We comprehensively catalog the immunomodulatory effects exerted by principal neuroregulatory mediators, categorized as: (1) neurotransmitters (glutamate, glutamine, γ-aminobutyric acid, epinephrine, norepinephrine, dopamine, serotonin, acetylcholine, and gaseous signaling molecules); (2) neuropeptides (substance P, calcitonin gene-related peptide, vasoactive intestinal peptide); and (3) neurotrophic factors. Furthermore, we critically evaluate the translational prospects and therapeutic challenges of targeting neuroimmune pathways and propose strategic priorities and research focuses for advancing the development of neuroimmune interaction-related therapeutic approaches in CRC.
{"title":"Decoding the neuroimmune axis in colorectal cancer: From neural circuitry to therapeutic innovation","authors":"Ying Li , Sheng-ya Yang , Ying-ru Zhang , Yan Wang","doi":"10.1016/j.cytogfr.2025.04.001","DOIUrl":"10.1016/j.cytogfr.2025.04.001","url":null,"abstract":"<div><div>The nervous and immune systems are two major components that maintain body homeostasis, with their functional roles often overlapping significantly. Both systems are capable of identifying, integrating, and organizing responsive reactions to various external stimuli. The gut, referred to as the \"second brain\" and the largest immune organ in the body, serves as the most frequent focal site for neuroimmune interactions. Colorectal cancer (CRC), as the predominant solid tumor arising in this neuroimmune-rich microenvironment, remains understudied through the lens of neuroimmune regulatory mechanisms. This review systematically synthesizes current evidence to elucidate the neuroimmune axis in CRC pathogenesis, with particular emphasis on neuroimmune crosstalk-mediated remodeling of tumor immunity. We comprehensively catalog the immunomodulatory effects exerted by principal neuroregulatory mediators, categorized as: (1) neurotransmitters (glutamate, glutamine, γ-aminobutyric acid, epinephrine, norepinephrine, dopamine, serotonin, acetylcholine, and gaseous signaling molecules); (2) neuropeptides (substance P, calcitonin gene-related peptide, vasoactive intestinal peptide); and (3) neurotrophic factors. Furthermore, we critically evaluate the translational prospects and therapeutic challenges of targeting neuroimmune pathways and propose strategic priorities and research focuses for advancing the development of neuroimmune interaction-related therapeutic approaches in CRC.</div></div>","PeriodicalId":11132,"journal":{"name":"Cytokine & Growth Factor Reviews","volume":"83 ","pages":"Pages 3-17"},"PeriodicalIF":9.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143990169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-06-01Epub Date: 2025-05-10DOI: 10.1016/j.cytogfr.2025.05.001
Tara Shammas , Malalage N. Peiris , April N. Meyer , Daniel J. Donoghue
The chromosomal translocation t(9;22)(q34;q11), known as the Philadelphia (Ph) chromosome, results in the BCR-ABL gene fusion which gives rise to Chronic Myeloid Leukemia (CML), a slowly progressing hematopoietic cancer that begins in the bone marrow of the patient. Making up about 15 % of all new leukemia cases, CML remains a critical focus of cancer research and treatment due to its distinctive genetic hallmark, the BCR-ABL fusion gene. The BCR-ABL fusion protein is a constitutively active tyrosine kinase which signals to multiple pathways including the Ras/MAPK, PI3K/AKT, JAK/STAT and NF-kappaB pathways which promote uncontrolled cell proliferation and survival. While multiple tyrosine kinase inhibitors (TKIs) are used to specifically target the fusion in the treatment of CML, new therapies are becoming available to overcome the resistance that occurs during TKI treatments of the disease. The discovery of the Philadelphia chromosome and the subsequent elucidation of the BCR-ABL fusion protein have since become a paradigm for understanding the genetic basis of cancer and developing precision medicine approaches. This review highlights the etiology and historical discovery of the BCR-ABL fusion, recent advances in understanding its regulatory mechanisms, and emerging strategies for its therapeutic targeting.
{"title":"BCR-ABL: The molecular mastermind behind chronic myeloid leukemia","authors":"Tara Shammas , Malalage N. Peiris , April N. Meyer , Daniel J. Donoghue","doi":"10.1016/j.cytogfr.2025.05.001","DOIUrl":"10.1016/j.cytogfr.2025.05.001","url":null,"abstract":"<div><div>The chromosomal translocation t(9;22)(q34;q11), known as the Philadelphia (Ph) chromosome, results in the <em>BCR-ABL</em> gene fusion which gives rise to Chronic Myeloid Leukemia (CML), a slowly progressing hematopoietic cancer that begins in the bone marrow of the patient. Making up about 15 % of all new leukemia cases, CML remains a critical focus of cancer research and treatment due to its distinctive genetic hallmark, the <em>BCR-ABL</em> fusion gene. The BCR-ABL fusion protein is a constitutively active tyrosine kinase which signals to multiple pathways including the Ras/MAPK, PI3K/AKT, JAK/STAT and NF-kappaB pathways which promote uncontrolled cell proliferation and survival. While multiple tyrosine kinase inhibitors (TKIs) are used to specifically target the fusion in the treatment of CML, new therapies are becoming available to overcome the resistance that occurs during TKI treatments of the disease. The discovery of the Philadelphia chromosome and the subsequent elucidation of the BCR-ABL fusion protein have since become a paradigm for understanding the genetic basis of cancer and developing precision medicine approaches. This review highlights the etiology and historical discovery of the BCR-ABL fusion, recent advances in understanding its regulatory mechanisms, and emerging strategies for its therapeutic targeting.</div></div>","PeriodicalId":11132,"journal":{"name":"Cytokine & Growth Factor Reviews","volume":"83 ","pages":"Pages 45-58"},"PeriodicalIF":9.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144062700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-04-01Epub Date: 2024-09-02DOI: 10.1016/j.cytogfr.2024.08.004
Francesca Coperchini , Alessia Greco , Marsida Teliti , Laura Croce , Spyridon Chytiris , Flavia Magri , Carlo Gaetano , Mario Rotondi
Population ageing is increasing in prevalence in most developed countries. Ageing is the decline of functional properties at the cellular, tissue, and organ level. Biochemical changes that occur in all organisms that experience biological ageing are referred to as the “Hallmarks of ageing”. Inflammation is a common denominator of the hallmarks of ageing, being mechanistically involved in most age-related health consequences. Inflamm-ageing refers to age-related changes in the inflammatory and immune systems which somehow drive the ageing process towards healthy or unhealthy ageing. Current evidences, support that, reversing the age-related pro-inflammatory status of inflamm-ageing, is able to modulate most hallmarks of ageing. Inflamm-ageing is associated with increased levels of pro-inflammatory molecules (e.g. cytokines, chemokines), ultimately producing a chronic low-grade inflammatory state typically observed in older individuals. It is commonly accepted that, the balance between pro- and anti-inflammatory cytokines/chemokines is one of the factors determining whether healthy or unhealthy ageing occurs. Malnutrition and nutritional imbalances, are highly prevalent in the elderly, playing a role in driving the balance of pro- and anti-inflammatory immunoactive molecules. In particular, malnutrition is a major risk factor for sarcopenia, a phenomenon characterized by loss of muscle mass, which is often referred to as the biological basis for frailty. Given the close relationship between malnutrition and sarcopenia, there is also evidence for a link between malnutrition and frailty. Indeed, changes in cytokine/chemokine levels in elderly patients with malnutrition were demonstrated. The demonstration that specific cytokines play a role in modulating appetite and nutrient sensing and taste reception, provided further evidence for the existence of a link between inflamm-ageing, nutrition and cytokines in shaping the trajectory of ageing. The present review will overview current evidence supporting the role of specific circulating cytokines and chemokines in the relationship between ageing, inflammation, and malnutrition.
{"title":"Inflamm-ageing: How cytokines and nutrition shape the trajectory of ageing","authors":"Francesca Coperchini , Alessia Greco , Marsida Teliti , Laura Croce , Spyridon Chytiris , Flavia Magri , Carlo Gaetano , Mario Rotondi","doi":"10.1016/j.cytogfr.2024.08.004","DOIUrl":"10.1016/j.cytogfr.2024.08.004","url":null,"abstract":"<div><div>Population ageing is increasing in prevalence in most developed countries. Ageing is the decline of functional properties at the cellular, tissue, and organ level. Biochemical changes that occur in all organisms that experience biological ageing are referred to as the “Hallmarks of ageing”. Inflammation is a common denominator of the hallmarks of ageing, being mechanistically involved in most age-related health consequences. Inflamm-ageing refers to age-related changes in the inflammatory and immune systems which somehow drive the ageing process towards healthy or unhealthy ageing. Current evidences, support that, reversing the age-related pro-inflammatory status of inflamm-ageing, is able to modulate most hallmarks of ageing. Inflamm-ageing is associated with increased levels of pro-inflammatory molecules (e.g. cytokines, chemokines), ultimately producing a chronic low-grade inflammatory state typically observed in older individuals. It is commonly accepted that, the balance between pro- and anti-inflammatory cytokines/chemokines is one of the factors determining whether healthy or unhealthy ageing occurs. Malnutrition and nutritional imbalances, are highly prevalent in the elderly, playing a role in driving the balance of pro- and anti-inflammatory immunoactive molecules. In particular, malnutrition is a major risk factor for sarcopenia, a phenomenon characterized by loss of muscle mass, which is often referred to as the biological basis for frailty. Given the close relationship between malnutrition and sarcopenia, there is also evidence for a link between malnutrition and frailty. Indeed, changes in cytokine/chemokine levels in elderly patients with malnutrition were demonstrated. The demonstration that specific cytokines play a role in modulating appetite and nutrient sensing and taste reception, provided further evidence for the existence of a link between inflamm-ageing, nutrition and cytokines in shaping the trajectory of ageing. The present review will overview current evidence supporting the role of specific circulating cytokines and chemokines in the relationship between ageing, inflammation, and malnutrition.</div></div>","PeriodicalId":11132,"journal":{"name":"Cytokine & Growth Factor Reviews","volume":"82 ","pages":"Pages 31-42"},"PeriodicalIF":9.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142139581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chronic Obstructive Pulmonary Disease (COPD) is a poorly reversible respiratory disorder distinguished by dyspnea, cough, expectoration and exacerbations due to abnormality of airways or emphysema. In this review, we consider the therapeutic potential of targeting Mammalian target of Rapamycin (mTOR) for treating COPD. The mTOR is a highly conserved serine-threonine protein kinase that integrates signals from growth factors and nutrients to control protein synthesis, lipid biogenesis and metabolism. Dysregulated mTOR pathway signaling due to genetic factors or cigarette smoking impairs autophagy, driving the buildup of abnormal cells and damaged proteins, resulting in inflammation and oxidative stress. Persistent mTOR activation also contributes to pulmonary vascular cell proliferation, facilitating the development of pulmonary resistance in COPD. Rapamycin, an inhibitor of mTOR, prevents the buildup of senescent cells in the lungs of COPD patients and inhibits the release of lung tissue-damaging proteases. mTOR also impacts the corticosteroid sensitivity in COPD patients by regulating the levels of histone deacetylases. The emerging role of gut-lung axis dysbiosis in the progression of COPD and its influence on mTOR further highlights the relevance of the mTOR pathway in COPD pathophysiology.
{"title":"Mechanisms coupling the mTOR pathway to chronic obstructive pulmonary disease (COPD) pathogenesis","authors":"Ankita Goyal , Vishal Chopra , Kranti Garg , Siddharth Sharma","doi":"10.1016/j.cytogfr.2024.12.005","DOIUrl":"10.1016/j.cytogfr.2024.12.005","url":null,"abstract":"<div><div>Chronic Obstructive Pulmonary Disease (COPD) is a poorly reversible respiratory disorder distinguished by dyspnea, cough, expectoration and exacerbations due to abnormality of airways or emphysema. In this review, we consider the therapeutic potential of targeting Mammalian target of Rapamycin (mTOR) for treating COPD. The mTOR is a highly conserved serine-threonine protein kinase that integrates signals from growth factors and nutrients to control protein synthesis, lipid biogenesis and metabolism. Dysregulated mTOR pathway signaling due to genetic factors or cigarette smoking impairs autophagy, driving the buildup of abnormal cells and damaged proteins, resulting in inflammation and oxidative stress. Persistent mTOR activation also contributes to pulmonary vascular cell proliferation, facilitating the development of pulmonary resistance in COPD. Rapamycin, an inhibitor of mTOR, prevents the buildup of senescent cells in the lungs of COPD patients and inhibits the release of lung tissue-damaging proteases. mTOR also impacts the corticosteroid sensitivity in COPD patients by regulating the levels of histone deacetylases. The emerging role of gut-lung axis dysbiosis in the progression of COPD and its influence on mTOR further highlights the relevance of the mTOR pathway in COPD pathophysiology.</div></div>","PeriodicalId":11132,"journal":{"name":"Cytokine & Growth Factor Reviews","volume":"82 ","pages":"Pages 55-69"},"PeriodicalIF":9.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142970020","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-04-01Epub Date: 2024-10-09DOI: 10.1016/j.cytogfr.2024.10.001
Suprabhat Mukherjee , Jagadeesh Bayry
Various pattern recognition receptors (PRRs), including toll-like receptors (TLRs), play a crucial role in recognizing invading pathogens as well as damage-associated molecular patterns (DAMPs) released in response to infection. The resulting signaling cascades initiate appropriate immune responses to eliminate these pathogens. Current evidence suggests that SARS-CoV-2-driven activation of TLR4, whether through direct recognition of the spike glycoprotein (alone or in combination with endotoxin) or by sensing various TLR4-activating DAMPs or alarmins released during viral infection, acts as a critical mediator of antiviral immunity. However, TLR4 exerts a dual role in COVID-19, demonstrating both beneficial and deleterious effects. Dysregulated TLR4 signaling is implicated in the proinflammatory consequences linked to the immunopathogenesis of COVID-19. Additionally, TLR4 polymorphisms contribute to severity of the disease. Given its significant immunoregulatory impact on COVID-19 immunopathology and host immunity, TLR4 has emerged as a key target for developing inhibitors and immunotherapeutic strategies to mitigate the adverse effects associated with SARS-CoV-2 and related infections. Furthermore, TLR4 agonists are also being explored as adjuvants to enhance immune responses to SARS-CoV-2 vaccines.
{"title":"The Yin and Yang of TLR4 in COVID-19","authors":"Suprabhat Mukherjee , Jagadeesh Bayry","doi":"10.1016/j.cytogfr.2024.10.001","DOIUrl":"10.1016/j.cytogfr.2024.10.001","url":null,"abstract":"<div><div>Various pattern recognition receptors (PRRs), including toll-like receptors (TLRs), play a crucial role in recognizing invading pathogens as well as damage-associated molecular patterns (DAMPs) released in response to infection. The resulting signaling cascades initiate appropriate immune responses to eliminate these pathogens. Current evidence suggests that SARS-CoV-2-driven activation of TLR4, whether through direct recognition of the spike glycoprotein (alone or in combination with endotoxin) or by sensing various TLR4-activating DAMPs or alarmins released during viral infection, acts as a critical mediator of antiviral immunity. However, TLR4 exerts a dual role in COVID-19, demonstrating both beneficial and deleterious effects. Dysregulated TLR4 signaling is implicated in the proinflammatory consequences linked to the immunopathogenesis of COVID-19. Additionally, TLR4 polymorphisms contribute to severity of the disease. Given its significant immunoregulatory impact on COVID-19 immunopathology and host immunity, TLR4 has emerged as a key target for developing inhibitors and immunotherapeutic strategies to mitigate the adverse effects associated with SARS-CoV-2 and related infections. Furthermore, TLR4 agonists are also being explored as adjuvants to enhance immune responses to SARS-CoV-2 vaccines.</div></div>","PeriodicalId":11132,"journal":{"name":"Cytokine & Growth Factor Reviews","volume":"82 ","pages":"Pages 70-85"},"PeriodicalIF":9.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567799","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-04-01Epub Date: 2024-08-23DOI: 10.1016/j.cytogfr.2024.08.005
Yuheng Song , Jiani Lu , Pengcheng Qin , Hongzhuan Chen , Lili Chen
The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to pose a significant global public health threat, particularly to older adults, pregnant women, and individuals with underlying chronic conditions. Dysregulated immune responses to SARS-CoV-2 infection are believed to contribute to the progression of COVID-19 in severe cases. Previous studies indicates that a deficiency in type I interferon (IFN-I) immunity accounts for approximately 15 %-20 % of patients with severe pneumonia caused by COVID-19, highlighting the potential therapeutic importance of modulating IFN-I signals. Natural products and their derivatives, due to their structural diversity and novel scaffolds, play a crucial role in drug discovery. Some of these natural products targeting IFN-I have demonstrated applications in infectious diseases and inflammatory conditions. However, the immunomodulatory potential of IFN-I in critical COVID-19 pneumonia and the natural compounds regulating the related signal pathway remain not fully understood. In this review, we offer a comprehensive assessment of the association between IFN-I and severe COVID-19, exploring its mechanisms and integrating information on natural compounds effective for IFN-I regulation. Focusing on the primary targets of IFN-I, we also summarize the regulatory mechanisms of natural products, their impact on IFNs, and their therapeutic roles in viral infections. Collectively, by synthesizing these findings, our goal is to provide a valuable reference for future research and to inspire innovative treatment strategies for COVID-19.
{"title":"Interferon-I modulation and natural products: Unraveling mechanisms and therapeutic potential in severe COVID-19","authors":"Yuheng Song , Jiani Lu , Pengcheng Qin , Hongzhuan Chen , Lili Chen","doi":"10.1016/j.cytogfr.2024.08.005","DOIUrl":"10.1016/j.cytogfr.2024.08.005","url":null,"abstract":"<div><div>The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to pose a significant global public health threat, particularly to older adults, pregnant women, and individuals with underlying chronic conditions. Dysregulated immune responses to SARS-CoV-2 infection are believed to contribute to the progression of COVID-19 in severe cases. Previous studies indicates that a deficiency in type I interferon (IFN-I) immunity accounts for approximately 15 %-20 % of patients with severe pneumonia caused by COVID-19, highlighting the potential therapeutic importance of modulating IFN-I signals. Natural products and their derivatives, due to their structural diversity and novel scaffolds, play a crucial role in drug discovery. Some of these natural products targeting IFN-I have demonstrated applications in infectious diseases and inflammatory conditions. However, the immunomodulatory potential of IFN-I in critical COVID-19 pneumonia and the natural compounds regulating the related signal pathway remain not fully understood. In this review, we offer a comprehensive assessment of the association between IFN-I and severe COVID-19, exploring its mechanisms and integrating information on natural compounds effective for IFN-I regulation. Focusing on the primary targets of IFN-I, we also summarize the regulatory mechanisms of natural products, their impact on IFNs, and their therapeutic roles in viral infections. Collectively, by synthesizing these findings, our goal is to provide a valuable reference for future research and to inspire innovative treatment strategies for COVID-19.</div></div>","PeriodicalId":11132,"journal":{"name":"Cytokine & Growth Factor Reviews","volume":"82 ","pages":"Pages 18-30"},"PeriodicalIF":9.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142189275","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-04-01Epub Date: 2024-08-14DOI: 10.1016/j.cytogfr.2024.08.002
Altijana Hromić-Jahjefendić , Lejla Mahmutović , Abas Sezer , Tea Bećirević , Alberto Rubio-Casillas , Elrashdy M. Redwan , Vladimir N. Uversky
Long COVID-19 affects a significant percentage of patients and is characterized by a wide range of symptoms, including weariness and mental fog as well as emotional symptoms like worry and sadness. COVID-19 is closely linked to the autoimmune disorders that are becoming more prevalent worldwide and are linked to immune system hyperactivation, neutrophil extracellular trap (NET) development, and molecular mimicry pathways. Long-term COVID-related autoimmune responses include a watchful immune system referring to the ability of immune system to constantly monitor the body for signs of infection, disease, or abnormal cells; altered innate and adaptive immune cells, autoantigens secreted by living or dead neutrophils, and high concentrations of autoantibodies directed against different proteins. The microbiome, which consists of billions of bacteria living in the human body, is essential for controlling immune responses and supporting overall health. The microbiome can affect the course of long COVID-associated autoimmunity, including the degree of illness, the rate of recovery, and the onset of autoimmune reactions. Although the precise role of the microbiome in long COVID autoimmunity is still being investigated, new studies indicate that probiotics, prebiotics, and dietary changes—interventions that target the microbiome—may be able to reduce autoimmune reactions and enhance long-term outcomes for COVID-19 survivors. More research is required to precisely understand how the microbiome affects COVID-19-related autoimmunity and to create tailored treatment plans.
{"title":"The intersection of microbiome and autoimmunity in long COVID-19: Current insights and future directions","authors":"Altijana Hromić-Jahjefendić , Lejla Mahmutović , Abas Sezer , Tea Bećirević , Alberto Rubio-Casillas , Elrashdy M. Redwan , Vladimir N. Uversky","doi":"10.1016/j.cytogfr.2024.08.002","DOIUrl":"10.1016/j.cytogfr.2024.08.002","url":null,"abstract":"<div><div>Long COVID-19 affects a significant percentage of patients and is characterized by a wide range of symptoms, including weariness and mental fog as well as emotional symptoms like worry and sadness. COVID-19 is closely linked to the autoimmune disorders that are becoming more prevalent worldwide and are linked to immune system hyperactivation, neutrophil extracellular trap (NET) development, and molecular mimicry pathways. Long-term COVID-related autoimmune responses include a watchful immune system referring to the ability of immune system to constantly monitor the body for signs of infection, disease, or abnormal cells; altered innate and adaptive immune cells, autoantigens secreted by living or dead neutrophils, and high concentrations of autoantibodies directed against different proteins. The microbiome, which consists of billions of bacteria living in the human body, is essential for controlling immune responses and supporting overall health. The microbiome can affect the course of long COVID-associated autoimmunity, including the degree of illness, the rate of recovery, and the onset of autoimmune reactions. Although the precise role of the microbiome in long COVID autoimmunity is still being investigated, new studies indicate that probiotics, prebiotics, and dietary changes—interventions that target the microbiome—may be able to reduce autoimmune reactions and enhance long-term outcomes for COVID-19 survivors. More research is required to precisely understand how the microbiome affects COVID-19-related autoimmunity and to create tailored treatment plans.</div></div>","PeriodicalId":11132,"journal":{"name":"Cytokine & Growth Factor Reviews","volume":"82 ","pages":"Pages 43-54"},"PeriodicalIF":9.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142046453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-04-01Epub Date: 2025-01-02DOI: 10.1016/j.cytogfr.2024.12.003
Luka Hiti , Tijana Markovič , Mitja Lainscak , Jerneja Farkaš Lainščak , Emil Pal , Irena Mlinarič-Raščan
A cytokine storm is marked by excessive pro-inflammatory cytokine release, and has emerged as a key factor in severe COVID-19 cases – making it a critical therapeutic target. However, its pathophysiology was poorly understood, which hindered effective treatment. SARS-CoV-2 initially disrupts angiotensin signalling, promoting inflammation through ACE-2 downregulation. Some patients’ immune systems then fail to shift from innate to adaptive immunity, suppressing interferon responses and leading to excessive pyroptosis and neutrophil activation. This amplifies tissue damage and inflammation, creating a pro-inflammatory loop. The result is the disruption of Th1/Th2 and Th17/Treg balances, lymphocyte exhaustion, and extensive blood clotting. Cytokine storm treatments include glucocorticoids to suppress the immune system, monoclonal antibodies to neutralize specific cytokines, and JAK inhibitors to block cytokine receptor signalling. However, the most effective treatment options for mitigating SARS-CoV-2 infection remain vaccines as a preventive measure and antiviral drugs for the early stages of infection. This article synthesizes insights into immune dysregulation in COVID-19, offering a framework to better understand cytokine storms and to improve monitoring, biomarker discovery, and treatment strategies for COVID-19 and other conditions involving cytokine storms.
{"title":"The immunopathogenesis of a cytokine storm: The key mechanisms underlying severe COVID-19","authors":"Luka Hiti , Tijana Markovič , Mitja Lainscak , Jerneja Farkaš Lainščak , Emil Pal , Irena Mlinarič-Raščan","doi":"10.1016/j.cytogfr.2024.12.003","DOIUrl":"10.1016/j.cytogfr.2024.12.003","url":null,"abstract":"<div><div>A cytokine storm is marked by excessive pro-inflammatory cytokine release, and has emerged as a key factor in severe COVID-19 cases – making it a critical therapeutic target. However, its pathophysiology was poorly understood, which hindered effective treatment. SARS-CoV-2 initially disrupts angiotensin signalling, promoting inflammation through ACE-2 downregulation. Some patients’ immune systems then fail to shift from innate to adaptive immunity, suppressing interferon responses and leading to excessive pyroptosis and neutrophil activation. This amplifies tissue damage and inflammation, creating a pro-inflammatory loop. The result is the disruption of Th1/Th2 and Th17/Treg balances, lymphocyte exhaustion, and extensive blood clotting. Cytokine storm treatments include glucocorticoids to suppress the immune system, monoclonal antibodies to neutralize specific cytokines, and JAK inhibitors to block cytokine receptor signalling. However, the most effective treatment options for mitigating SARS-CoV-2 infection remain vaccines as a preventive measure and antiviral drugs for the early stages of infection. This article synthesizes insights into immune dysregulation in COVID-19, offering a framework to better understand cytokine storms and to improve monitoring, biomarker discovery, and treatment strategies for COVID-19 and other conditions involving cytokine storms.</div></div>","PeriodicalId":11132,"journal":{"name":"Cytokine & Growth Factor Reviews","volume":"82 ","pages":"Pages 1-17"},"PeriodicalIF":9.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143064253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01Epub Date: 2024-11-23DOI: 10.1016/j.cytogfr.2024.11.007
Jun Zhou , Ping Yan , Wenxue Ma , Jing Li
Uterine natural killer (uNK) cells play a pivotal role in promoting placental development and supporting maternal-fetal immune tolerance, primarily through cytokine regulation and growth factor production. While the importance of uNK cells in pregnancy is well-established, the mechanisms of their interactions with trophoblasts and contributions to various pregnancy complications remain incompletely understood. This review highlights recent advancements in understanding uNK cell functions, with a focus on cytokine production, growth factor secretion, and receptor-ligand interactions, particularly involving killer immunoglobulin-like receptors (KIR) and human leukocyte antigen-C (HLA-C). We explore how uNK cell dysfunction contributes to pregnancy complications, including preeclampsia, recurrent pregnancy loss, and placenta accreta spectrum (PAS) disorders, emphasizing their roles in immune tolerance and placental health. By detailing the distinct cytokine signaling pathways and functional subtypes of uNK cells, this review provides insights into their regulatory mechanisms essential for pregnancy maintenance. Additionally, we discuss emerging therapeutic strategies targeting uNK-trophoblast interactions and propose future research directions, including the development of non-invasive biomarkers and personalized interventions. This comprehensive review addresses critical knowledge gaps, aiming to advance research in reproductive immunology and guide therapeutic innovations in maternal health.
{"title":"Cytokine modulation and immunoregulation of uterine NK cells in pregnancy disorders","authors":"Jun Zhou , Ping Yan , Wenxue Ma , Jing Li","doi":"10.1016/j.cytogfr.2024.11.007","DOIUrl":"10.1016/j.cytogfr.2024.11.007","url":null,"abstract":"<div><div>Uterine natural killer (uNK) cells play a pivotal role in promoting placental development and supporting maternal-fetal immune tolerance, primarily through cytokine regulation and growth factor production. While the importance of uNK cells in pregnancy is well-established, the mechanisms of their interactions with trophoblasts and contributions to various pregnancy complications remain incompletely understood. This review highlights recent advancements in understanding uNK cell functions, with a focus on cytokine production, growth factor secretion, and receptor-ligand interactions, particularly involving killer immunoglobulin-like receptors (KIR) and human leukocyte antigen-C (HLA-C). We explore how uNK cell dysfunction contributes to pregnancy complications, including preeclampsia, recurrent pregnancy loss, and placenta accreta spectrum (PAS) disorders, emphasizing their roles in immune tolerance and placental health. By detailing the distinct cytokine signaling pathways and functional subtypes of uNK cells, this review provides insights into their regulatory mechanisms essential for pregnancy maintenance. Additionally, we discuss emerging therapeutic strategies targeting uNK-trophoblast interactions and propose future research directions, including the development of non-invasive biomarkers and personalized interventions. This comprehensive review addresses critical knowledge gaps, aiming to advance research in reproductive immunology and guide therapeutic innovations in maternal health.</div></div>","PeriodicalId":11132,"journal":{"name":"Cytokine & Growth Factor Reviews","volume":"81 ","pages":"Pages 40-53"},"PeriodicalIF":9.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142738728","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01Epub Date: 2024-12-12DOI: 10.1016/j.cytogfr.2024.11.006
Yan Chen , Hong Yi , Shan Liao , Junyu He , Yanhong Zhou , Yan Lei
Microtubule-associated protein 1 light chain 3B (MAP1LC3B, also known as LC3B) is a mammalian homolog of the autophagy-related protein 8 (ATG8) family. It plays a crucial role in cellular autophagy and is involved in several vital biological processes, including apoptosis and differentiation. Additionally, LC3B regulates immune responses. Due to its close association with malignant tumors and neurodegenerative diseases, and its potential as a prognostic indicator and therapeutic target, LC3B has become a significant research focus. This article aims to provide a comprehensive and systematic understanding of LC3B's role and mechanisms in autophagy, its impact on apoptosis and the underlying mechanisms, its regulation of cellular differentiation and transdifferentiation, its modulation of immune and inflammatory responses, the influence of upstream regulatory factors on LC3B's function, and its relevance to disease diagnosis, treatment, and prognosis. The goal is to establish a solid foundation for understanding LC3B's role in cellular processes and its regulatory mechanisms.
{"title":"LC3B: A microtubule-associated protein influences disease progression and prognosis","authors":"Yan Chen , Hong Yi , Shan Liao , Junyu He , Yanhong Zhou , Yan Lei","doi":"10.1016/j.cytogfr.2024.11.006","DOIUrl":"10.1016/j.cytogfr.2024.11.006","url":null,"abstract":"<div><div>Microtubule-associated protein 1 light chain 3B (MAP1LC3B, also known as LC3B) is a mammalian homolog of the autophagy-related protein 8 (ATG8) family. It plays a crucial role in cellular autophagy and is involved in several vital biological processes, including apoptosis and differentiation. Additionally, LC3B regulates immune responses. Due to its close association with malignant tumors and neurodegenerative diseases, and its potential as a prognostic indicator and therapeutic target, LC3B has become a significant research focus. This article aims to provide a comprehensive and systematic understanding of LC3B's role and mechanisms in autophagy, its impact on apoptosis and the underlying mechanisms, its regulation of cellular differentiation and transdifferentiation, its modulation of immune and inflammatory responses, the influence of upstream regulatory factors on LC3B's function, and its relevance to disease diagnosis, treatment, and prognosis. The goal is to establish a solid foundation for understanding LC3B's role in cellular processes and its regulatory mechanisms.</div></div>","PeriodicalId":11132,"journal":{"name":"Cytokine & Growth Factor Reviews","volume":"81 ","pages":"Pages 16-26"},"PeriodicalIF":9.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142863556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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