Pub Date : 2023-11-24DOI: 10.33696/immunology.5.177
Brittany S. Bruggeman, Desmond A. Schatz
Type 1 diabetes has historically been described as an endocrine (β-cell) specific autoimmune disease. However, a substantial reduction (20-50%) in pancreas organ size and subclinical to symptomatic exocrine pancreatic insufficiency are present at diagnosis and may begin even prior to the development of islet autoimmunity. The mechanisms of exocrine loss in type 1 diabetes are not well understood, but leading hypotheses include developmental defects, β-cell loss resulting in exocrine atrophy, or autoimmune or inflammatory destruction of exocrine cells. Inflammatory changes including acute and chronic pancreatitis, exocrine T cell infiltration and classical complement activation, and serum exocrine autoantibodies within type 1 diabetes individuals suggest that an autoimmune or inflammatory process may contribute to exocrine pancreatic dysfunction. Exocrine pancreas atrophy primarily occurs prior to the onset of clinical disease. Indeed, recent work implicates exocrine-specific alterations in gene and protein expression as key in type 1 diabetes development. Measures of exocrine size and function could be useful additions in the prediction of disease onset and in identifying potential therapeutic responders to disease therapies, however, this is an underdeveloped area of research. Additionally, exocrine pancreatic insufficiency is underdiagnosed in individuals with type 1 diabetes and individualized treatment protocols are lacking. Much work remains to be done in this area, but we can definitively say that type 1 diabetes is a disorder of both the exocrine and endocrine pancreas likely from the start.
{"title":"Type 1 Diabetes: A Disorder of the Exocrine and Endocrine Pancreas","authors":"Brittany S. Bruggeman, Desmond A. Schatz","doi":"10.33696/immunology.5.177","DOIUrl":"https://doi.org/10.33696/immunology.5.177","url":null,"abstract":"Type 1 diabetes has historically been described as an endocrine (β-cell) specific autoimmune disease. However, a substantial reduction (20-50%) in pancreas organ size and subclinical to symptomatic exocrine pancreatic insufficiency are present at diagnosis and may begin even prior to the development of islet autoimmunity. The mechanisms of exocrine loss in type 1 diabetes are not well understood, but leading hypotheses include developmental defects, β-cell loss resulting in exocrine atrophy, or autoimmune or inflammatory destruction of exocrine cells. Inflammatory changes including acute and chronic pancreatitis, exocrine T cell infiltration and classical complement activation, and serum exocrine autoantibodies within type 1 diabetes individuals suggest that an autoimmune or inflammatory process may contribute to exocrine pancreatic dysfunction. Exocrine pancreas atrophy primarily occurs prior to the onset of clinical disease. Indeed, recent work implicates exocrine-specific alterations in gene and protein expression as key in type 1 diabetes development. Measures of exocrine size and function could be useful additions in the prediction of disease onset and in identifying potential therapeutic responders to disease therapies, however, this is an underdeveloped area of research. Additionally, exocrine pancreatic insufficiency is underdiagnosed in individuals with type 1 diabetes and individualized treatment protocols are lacking. Much work remains to be done in this area, but we can definitively say that type 1 diabetes is a disorder of both the exocrine and endocrine pancreas likely from the start.","PeriodicalId":73644,"journal":{"name":"Journal of cellular immunology","volume":"904 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139242226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Systemic lupus erythematosus (SLE) is a common autoimmune disease caused by multiple factors. The pathogenesis of SLE remains unclear. Helper T cell 2 (Th2 cell) is essential for humoral immunity, which participates in regulating type 2 immune response by producing typical cytokines of interleukin (IL)-4, IL-5, and IL-13. It is well known that Th2-associated immunity plays a vital role in autoimmune diseases, including SLE. However, current progress on the role and potential mechanism of Th2-associated immunity in SLE remains largely unknown. The work by Wang et al. have provided an in-depth association of Th2-associated immunity with SLE and the clinical application perspectives. We provide a more comprehensive and up-to-date commentary on Th2-associated immunity in regulating SLE to explore new therapeutic targets.
{"title":"Commentary on Updated Insight into the Role of Th2-Associated Immunity in Systemic Lupus Erythematosus","authors":"Xinyue Hou, Jinjin Chu, Shuhao Liu, Shuyu Jin, Jiamei Sun, Hui Wang, Haibo Li, Wei Liu, Chunxiang Chai, Sue Zhang, Donghua Xu","doi":"10.33696/immunology.5.176","DOIUrl":"https://doi.org/10.33696/immunology.5.176","url":null,"abstract":"Systemic lupus erythematosus (SLE) is a common autoimmune disease caused by multiple factors. The pathogenesis of SLE remains unclear. Helper T cell 2 (Th2 cell) is essential for humoral immunity, which participates in regulating type 2 immune response by producing typical cytokines of interleukin (IL)-4, IL-5, and IL-13. It is well known that Th2-associated immunity plays a vital role in autoimmune diseases, including SLE. However, current progress on the role and potential mechanism of Th2-associated immunity in SLE remains largely unknown. The work by Wang et al. have provided an in-depth association of Th2-associated immunity with SLE and the clinical application perspectives. We provide a more comprehensive and up-to-date commentary on Th2-associated immunity in regulating SLE to explore new therapeutic targets.","PeriodicalId":73644,"journal":{"name":"Journal of cellular immunology","volume":"23 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136034771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-10-17DOI: 10.33696/immunology.5.175
Kamen W. Kossow, Joseph G. Bennett, Marc S Hoffmann
Treatment of lymphomas involves a wide variety of chemotherapy, immunotherapy, and targeted-agents tailored to disease biology and patient characteristics. Each of these regimens carry their own risk of opportunistic infections in an immunocompromised population. In addition to the treatment associated immunosuppression, lymphoma itself is immunosuppressive. Lymphoma associated immunosuppression is secondary to increased production of abnormal lymphocytes resulting in decreased production of normally functioning lymphocytes. Additionally, lymphoma cells induce both humoral and cellular immunosuppression through effects on numerous cytokines, T-cells, myeloid-derived suppressor cells, and macrophages. Clinical trials, patient co-morbidities, and institutional preferences all play a role in determining the preferred antimicrobial prophylaxis. While there is a paucity of data on systematic reviews and guidelines for standardized chemotherapy regimens in lymphoma patients, the efficacy and recommendations for antimicrobial prophylaxis in specific chemotherapy regimens for lymphoma has not been fully reviewed. According to the National Comprehensive Cancer Network, lymphoma is generally regarded as an ‘intermediate risk’ cancer with regards to overall infection risk. This results in discordance between research data and clinical practice. This is reiterated in the SIGNIFICANT trial which reported that while guidelines previously advised against fluoroquinolone prophylaxis in lymphoma and solid cancers, a survey of 3,600 physicians revealed that 45% routinely used fluoroquinolone prophylaxis despite these recommendations. This review article analyzes numerous research studies with summarization of findings and antimicrobial prophylaxis recommendations based on specific lymphoma chemotherapy regimens. With regards to each specific chemotherapy regimen assessed, indications for antibacterial, anti-viral, anti-fungal, and Pneumocystis jiroveci pneumonia (PJP) prophylaxis were determined for each regimen. The degree of immunosuppression and the necessary prophylaxis varies across different regimens and lymphoma subgroups; and thus, an individualized approach is necessary to optimize the supportive care during lymphoma treatment.
{"title":"Antimicrobial Prophylaxis in Lymphoma by Chemotherapy Regimen","authors":"Kamen W. Kossow, Joseph G. Bennett, Marc S Hoffmann","doi":"10.33696/immunology.5.175","DOIUrl":"https://doi.org/10.33696/immunology.5.175","url":null,"abstract":"Treatment of lymphomas involves a wide variety of chemotherapy, immunotherapy, and targeted-agents tailored to disease biology and patient characteristics. Each of these regimens carry their own risk of opportunistic infections in an immunocompromised population. In addition to the treatment associated immunosuppression, lymphoma itself is immunosuppressive. Lymphoma associated immunosuppression is secondary to increased production of abnormal lymphocytes resulting in decreased production of normally functioning lymphocytes. Additionally, lymphoma cells induce both humoral and cellular immunosuppression through effects on numerous cytokines, T-cells, myeloid-derived suppressor cells, and macrophages. Clinical trials, patient co-morbidities, and institutional preferences all play a role in determining the preferred antimicrobial prophylaxis. While there is a paucity of data on systematic reviews and guidelines for standardized chemotherapy regimens in lymphoma patients, the efficacy and recommendations for antimicrobial prophylaxis in specific chemotherapy regimens for lymphoma has not been fully reviewed. According to the National Comprehensive Cancer Network, lymphoma is generally regarded as an ‘intermediate risk’ cancer with regards to overall infection risk. This results in discordance between research data and clinical practice. This is reiterated in the SIGNIFICANT trial which reported that while guidelines previously advised against fluoroquinolone prophylaxis in lymphoma and solid cancers, a survey of 3,600 physicians revealed that 45% routinely used fluoroquinolone prophylaxis despite these recommendations. This review article analyzes numerous research studies with summarization of findings and antimicrobial prophylaxis recommendations based on specific lymphoma chemotherapy regimens. With regards to each specific chemotherapy regimen assessed, indications for antibacterial, anti-viral, anti-fungal, and Pneumocystis jiroveci pneumonia (PJP) prophylaxis were determined for each regimen. The degree of immunosuppression and the necessary prophylaxis varies across different regimens and lymphoma subgroups; and thus, an individualized approach is necessary to optimize the supportive care during lymphoma treatment.","PeriodicalId":73644,"journal":{"name":"Journal of cellular immunology","volume":"76 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136032641","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-10-03DOI: 10.33696/immunology.5.173
Kaveh Rahimi, Akram Ebrahimifar, Mehri Rahimi
The male reproductive system may be affected by the systemic infections of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The precise mechanisms of male reproductive impairment are not well known. There are two possible mechanisms for the effect of SARS-CoV-2 on the male reproductive system either directly through the impact of the angiotensin-converting enzyme 2 (ACE2) receptor on testicular tissue or indirectly through the effect of the secondary autoimmune response on testicular functions. The second mechanism is more likely. Extensive studies need to be conducted on the impact of SARS-CoV-2 on the functional characteristics of sperm and the results of natural fertilization or assisted reproductive technology.
{"title":"Would It be Possible for a SARS-CoV-2 Infection to Affect the Male Reproductive System?","authors":"Kaveh Rahimi, Akram Ebrahimifar, Mehri Rahimi","doi":"10.33696/immunology.5.173","DOIUrl":"https://doi.org/10.33696/immunology.5.173","url":null,"abstract":"The male reproductive system may be affected by the systemic infections of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The precise mechanisms of male reproductive impairment are not well known. There are two possible mechanisms for the effect of SARS-CoV-2 on the male reproductive system either directly through the impact of the angiotensin-converting enzyme 2 (ACE2) receptor on testicular tissue or indirectly through the effect of the secondary autoimmune response on testicular functions. The second mechanism is more likely. Extensive studies need to be conducted on the impact of SARS-CoV-2 on the functional characteristics of sperm and the results of natural fertilization or assisted reproductive technology.","PeriodicalId":73644,"journal":{"name":"Journal of cellular immunology","volume":"21 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135697313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-28DOI: 10.33696/immunology.5.172
Alison M Mackay
{"title":"Fluoxetine is Antimicrobial and Modulates the Antibiotic Resistance Status of Bacteria","authors":"Alison M Mackay","doi":"10.33696/immunology.5.172","DOIUrl":"https://doi.org/10.33696/immunology.5.172","url":null,"abstract":"","PeriodicalId":73644,"journal":{"name":"Journal of cellular immunology","volume":"24 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135387137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-27DOI: 10.33696/immunology.5.169
Eman M. Ragab, Abeer A. Khamis, Doaa M. El Gamal, Tarek M. Mohamed
Oxidative phosphorylation dysregulation (OXPHOS) has been demonstrated to be essential for the development of cancer. Therefore, it may be argued that chaperone and deacetylase activities modulate OXPHOS activity. For instance, a complicated network of interactions connects a cell’s bioenergetic features and neoplastic potential through the imbalance of sirtuin 3 (SIRT3) and succinate dehydrogenase (SDH) enzymatic activity in mitochondria. The studies outlined in this review indicate that targeting SDH regulators is a promising novel therapeutic strategy for this extremely resistant disease. Additionally, a viable therapeutic strategy may involve triggering the cell death mechanism in cancer cells by blocking mitochondrial metabolism with a natural substance. A naturally occurring flavonoid called naringenin (NAR) has been extensively investigated for its pharmacological properties, which include anti-tumor actions. However, due to its low bioavailability in this situation, nanoencapsulation is designed to improve NAR anticancer efficacy. NAR can be encapsulated by chitosan nanoparticles-TPP conjugates, thereby improving NAR cellular absorption and cytotoxicity against cancer cells. Consequently, we proposed naringenin nanoparticles as a novel therapeutic target for SDH regulators in cancer.
{"title":"The Regulation Impact of Naringenin-loaded Chitosan Nanoparticles on Succinate Dehydrogenase Activity in Cancer Cells","authors":"Eman M. Ragab, Abeer A. Khamis, Doaa M. El Gamal, Tarek M. Mohamed","doi":"10.33696/immunology.5.169","DOIUrl":"https://doi.org/10.33696/immunology.5.169","url":null,"abstract":"Oxidative phosphorylation dysregulation (OXPHOS) has been demonstrated to be essential for the development of cancer. Therefore, it may be argued that chaperone and deacetylase activities modulate OXPHOS activity. For instance, a complicated network of interactions connects a cell’s bioenergetic features and neoplastic potential through the imbalance of sirtuin 3 (SIRT3) and succinate dehydrogenase (SDH) enzymatic activity in mitochondria. The studies outlined in this review indicate that targeting SDH regulators is a promising novel therapeutic strategy for this extremely resistant disease. Additionally, a viable therapeutic strategy may involve triggering the cell death mechanism in cancer cells by blocking mitochondrial metabolism with a natural substance. A naturally occurring flavonoid called naringenin (NAR) has been extensively investigated for its pharmacological properties, which include anti-tumor actions. However, due to its low bioavailability in this situation, nanoencapsulation is designed to improve NAR anticancer efficacy. NAR can be encapsulated by chitosan nanoparticles-TPP conjugates, thereby improving NAR cellular absorption and cytotoxicity against cancer cells. Consequently, we proposed naringenin nanoparticles as a novel therapeutic target for SDH regulators in cancer.","PeriodicalId":73644,"journal":{"name":"Journal of cellular immunology","volume":"34 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135580787","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-08-02DOI: 10.33696/immunology.5.168
Wenjuan Zheng, Yu Tang, Mengwei Cheng, Cui Ma, X. Fei, W. Shi
Peripheral circulating B-lymphocytes and B-lymphocytes in the bone marrow (BM) show different responses to lymphotoxic or immunosuppressive agents. We explored the existence of a dysregulated distribution of B-lymphocytes between peripheral and BM compartments and the underlying mechanisms. The percentage of CXC chemokine receptor 4+ B (CXCR4+ B) cells was decreased in the peripheral blood (PB) and increased in the BM of MRL/lpr mice and SLE patients. CXC chemokine ligand 12 (CXCL12) production by BM osteoblasts (OBs) derived from MRL/lpr mice and SLE patients was higher than that obtained with C57BL/6 mice or healthy subjects. MRL/lpr-derived OBs demonstrated stronger chemotactic ability toward B-lymphocytes than control OBs, and more B-lymphocytes colocalized with OBs within the periosteal zone in MRL/lpr mice. Moreover, the CXCR4+ B cell percentages were negatively correlated with the serum immunoglobulin G concentration, and the BM CXCL12 levels were positively correlated with the systemic lupus erythematosus disease activity index score and anti-double stranded DNA titer and negatively correlated with the serum complement 3 concentration. In conclusion, our results indicate a shifted distribution of B-lymphocytes between the BM and peripheral compartments in SLE patients and MRL/lpr mice and that the upregulation of CXCL12 in OBs likely contributes to enhanced chemotactic migration and anchorage of B-lymphocytes to OBs.
外周血b淋巴细胞和骨髓b淋巴细胞(BM)对淋巴抑制剂或免疫抑制剂表现出不同的反应。我们探讨了b淋巴细胞在外周和骨髓间室分布失调的存在及其潜在机制。MRL/lpr小鼠和SLE患者外周血(PB)中CXC趋化因子受体4+ B (CXCR4+ B)细胞百分比降低，BM中CXCR4+ B细胞百分比升高。来自MRL/lpr小鼠和SLE患者的BM成骨细胞(OBs)产生的CXC趋化因子配体12 (CXCL12)高于C57BL/6小鼠或健康受试者。MRL/lpr衍生OBs对b淋巴细胞的趋化能力强于对照OBs, MRL/lpr小鼠骨膜带内OBs共定位的b淋巴细胞较多。CXCR4+ B细胞百分比与血清免疫球蛋白G浓度呈负相关，BM CXCL12水平与系统性红斑狼疮疾病活动性指数评分和抗双链DNA滴度呈正相关，与血清补体3浓度呈负相关。总之，我们的研究结果表明，在SLE患者和MRL/lpr小鼠中，b淋巴细胞在基底细胞和外周腔室之间的分布发生了转移，而ob中CXCL12的上调可能有助于b淋巴细胞向ob的趋化迁移和锚定增强。
{"title":"Dysregulated CXCL12 Expression in Osteoblasts Promotes B-lymphocytes Preferentially Homing to the Bone Marrow in MRL/lpr Mice","authors":"Wenjuan Zheng, Yu Tang, Mengwei Cheng, Cui Ma, X. Fei, W. Shi","doi":"10.33696/immunology.5.168","DOIUrl":"https://doi.org/10.33696/immunology.5.168","url":null,"abstract":"Peripheral circulating B-lymphocytes and B-lymphocytes in the bone marrow (BM) show different responses to lymphotoxic or immunosuppressive agents. We explored the existence of a dysregulated distribution of B-lymphocytes between peripheral and BM compartments and the underlying mechanisms. The percentage of CXC chemokine receptor 4+ B (CXCR4+ B) cells was decreased in the peripheral blood (PB) and increased in the BM of MRL/lpr mice and SLE patients. CXC chemokine ligand 12 (CXCL12) production by BM osteoblasts (OBs) derived from MRL/lpr mice and SLE patients was higher than that obtained with C57BL/6 mice or healthy subjects. MRL/lpr-derived OBs demonstrated stronger chemotactic ability toward B-lymphocytes than control OBs, and more B-lymphocytes colocalized with OBs within the periosteal zone in MRL/lpr mice. Moreover, the CXCR4+ B cell percentages were negatively correlated with the serum immunoglobulin G concentration, and the BM CXCL12 levels were positively correlated with the systemic lupus erythematosus disease activity index score and anti-double stranded DNA titer and negatively correlated with the serum complement 3 concentration. In conclusion, our results indicate a shifted distribution of B-lymphocytes between the BM and peripheral compartments in SLE patients and MRL/lpr mice and that the upregulation of CXCL12 in OBs likely contributes to enhanced chemotactic migration and anchorage of B-lymphocytes to OBs.","PeriodicalId":73644,"journal":{"name":"Journal of cellular immunology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46654472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-07-17DOI: 10.33696/immunology.5.167
Limei Xu, Xiangguo Liu
Abnormal activation of epidermal growth factor receptor (EGFR) promotes the development of Non-Small Cell Lung Cancer Cells (NSCLC). Chemoresistance to tyrosine kinase inhibitors (TKIs), which is elicited by EGFR mutations, is a key challenge for NSCLC treatment. In the present study, we demonstrate a critical role of gasdermin E (GSDME), an important protein for pyroptosis, in the maintenance of EGFR stability and activation. We found that GSDME depletion suppressed the EGFR-mediated proliferation of NSCLC cells in vitro. GSDME knockdown downregulated the protein level of CCND1 and inhibited the phosphorylation of ERK1/2 in NSCLC cells. Mechanistically, both GSDME-FL and GSDME-N fragment physically interacted with EGFR. GSDME interacted with cytoplasmic fragment (CT) of EGFR. GSDME knockdown inhibited EGFR dimerization and phosphorylation at tyrosine 1173 (EGFRY1173), which could activate ERK1/2. GSDME knockdown promoted EGFR degradation and phosphorylation at tyrosine 1045 (EGFRY1045). Importantly, GSDME-FL increased the stability of EGFR, while the GSDME-N fragment induced EGFR degradation. Together, our results demonstrate that the GSDME-EGFR interaction plays an important role in NSCLC development, reveal a previously unrecognized link between GSDME and EGFR stability and offer new insight into cancer pathogenesis.
{"title":"Sharing Weal and Woe: A Commentary on “Gasdermin E Regulates the Stability and Activation of EGFR in Human Non-Small Cell Lung Cancer Cells”","authors":"Limei Xu, Xiangguo Liu","doi":"10.33696/immunology.5.167","DOIUrl":"https://doi.org/10.33696/immunology.5.167","url":null,"abstract":"Abnormal activation of epidermal growth factor receptor (EGFR) promotes the development of Non-Small Cell Lung Cancer Cells (NSCLC). Chemoresistance to tyrosine kinase inhibitors (TKIs), which is elicited by EGFR mutations, is a key challenge for NSCLC treatment. In the present study, we demonstrate a critical role of gasdermin E (GSDME), an important protein for pyroptosis, in the maintenance of EGFR stability and activation. We found that GSDME depletion suppressed the EGFR-mediated proliferation of NSCLC cells in vitro. GSDME knockdown downregulated the protein level of CCND1 and inhibited the phosphorylation of ERK1/2 in NSCLC cells. Mechanistically, both GSDME-FL and GSDME-N fragment physically interacted with EGFR. GSDME interacted with cytoplasmic fragment (CT) of EGFR. GSDME knockdown inhibited EGFR dimerization and phosphorylation at tyrosine 1173 (EGFRY1173), which could activate ERK1/2. GSDME knockdown promoted EGFR degradation and phosphorylation at tyrosine 1045 (EGFRY1045). Importantly, GSDME-FL increased the stability of EGFR, while the GSDME-N fragment induced EGFR degradation. Together, our results demonstrate that the GSDME-EGFR interaction plays an important role in NSCLC development, reveal a previously unrecognized link between GSDME and EGFR stability and offer new insight into cancer pathogenesis.","PeriodicalId":73644,"journal":{"name":"Journal of cellular immunology","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44144853","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-05-24DOI: 10.33696/immunology.5.166
Bamgbose Timothy, J. de la Fuente
. Exploring the Potential of Probiotics in Boosting the Immune System's Response to Reduce the Severity of Malaria. J Cell Immunol. 2023;5
.探索益生菌在增强免疫系统反应以降低疟疾严重程度方面的潜力。细胞免疫学杂志。2023年；5.
{"title":"Exploring the Potential of Probiotics in Boosting the Immune System's Response to Reduce the Severity of Malaria","authors":"Bamgbose Timothy, J. de la Fuente","doi":"10.33696/immunology.5.166","DOIUrl":"https://doi.org/10.33696/immunology.5.166","url":null,"abstract":". Exploring the Potential of Probiotics in Boosting the Immune System's Response to Reduce the Severity of Malaria. J Cell Immunol. 2023;5","PeriodicalId":73644,"journal":{"name":"Journal of cellular immunology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44149643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-04-29DOI: 10.33696/immunology.5.165
José Guillermo Cabanillas López
The course of the COVID-19 pandemic has led to high mortality rates worldwide, which justifies the development of various research studies aimed at elucidating the physiopathological mechanisms involved in the development of lung injury associated with this disease. The angiotensin-converting enzyme 2 (ACE2) receptor plays a leading role as the viral anchoring point necessary for viral replication to begin, so a thorough understanding of the regulatory mechanisms of this receptor is vital. Similarly, the distribution of ACE2 will justify the injury caused by SARS-CoV-2. Macrophages play a more significant role in lung injury since they allow the SARS-CoV-2 virus to reach tissues lacking ACE2 receptors and cause significant tissue damage. Therefore, all factors that influence macrophage migration and mobilization will be considered risk factors for the development of severe lung injury in COVID-19.
{"title":"Is Interstitial Macrophage Mainly Responsible for Lung Injury in SARS-CoV-2 Infection?","authors":"José Guillermo Cabanillas López","doi":"10.33696/immunology.5.165","DOIUrl":"https://doi.org/10.33696/immunology.5.165","url":null,"abstract":"The course of the COVID-19 pandemic has led to high mortality rates worldwide, which justifies the development of various research studies aimed at elucidating the physiopathological mechanisms involved in the development of lung injury associated with this disease. The angiotensin-converting enzyme 2 (ACE2) receptor plays a leading role as the viral anchoring point necessary for viral replication to begin, so a thorough understanding of the regulatory mechanisms of this receptor is vital. Similarly, the distribution of ACE2 will justify the injury caused by SARS-CoV-2. Macrophages play a more significant role in lung injury since they allow the SARS-CoV-2 virus to reach tissues lacking ACE2 receptors and cause significant tissue damage. Therefore, all factors that influence macrophage migration and mobilization will be considered risk factors for the development of severe lung injury in COVID-19.","PeriodicalId":73644,"journal":{"name":"Journal of cellular immunology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47370156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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