Pub Date : 2021-06-17DOI: 10.1186/s41232-021-00172-9
Takahiro Konuma, Yukinori Okada
The prediction of disease risks is an essential part of personalized medicine, which includes early disease detection, prevention, and intervention. The polygenic risk score (PRS) has become the standard for quantifying genetic liability in predicting disease risks. PRS utilizes single-nucleotide polymorphisms (SNPs) with genetic risks elucidated by genome-wide association studies (GWASs) and is calculated as weighted sum scores of these SNPs with genetic risks using their effect sizes from GWASs as their weights. The utilities of PRS have been explored in many common diseases, such as cancer, coronary artery disease, obesity, and diabetes, and in various non-disease traits, such as clinical biomarkers. These applications demonstrated that PRS could identify a high-risk subgroup of these diseases as a predictive biomarker and provide information on modifiable risk factors driving health outcomes. On the other hand, there are several limitations to implementing PRSs in clinical practice, such as biased sensitivity for the ethnic background of PRS calculation and geographical differences even in the same population groups. Also, it remains unclear which method is the most suitable for the prediction with high accuracy among numerous PRS methods developed so far. Although further improvements of its comprehensiveness and generalizability will be needed for its clinical implementation in the future, PRS will be a powerful tool for therapeutic interventions and lifestyle recommendations in a wide range of diseases. Thus, it may ultimately improve the health of an entire population in the future.
{"title":"Statistical genetics and polygenic risk score for precision medicine.","authors":"Takahiro Konuma, Yukinori Okada","doi":"10.1186/s41232-021-00172-9","DOIUrl":"https://doi.org/10.1186/s41232-021-00172-9","url":null,"abstract":"<p><p>The prediction of disease risks is an essential part of personalized medicine, which includes early disease detection, prevention, and intervention. The polygenic risk score (PRS) has become the standard for quantifying genetic liability in predicting disease risks. PRS utilizes single-nucleotide polymorphisms (SNPs) with genetic risks elucidated by genome-wide association studies (GWASs) and is calculated as weighted sum scores of these SNPs with genetic risks using their effect sizes from GWASs as their weights. The utilities of PRS have been explored in many common diseases, such as cancer, coronary artery disease, obesity, and diabetes, and in various non-disease traits, such as clinical biomarkers. These applications demonstrated that PRS could identify a high-risk subgroup of these diseases as a predictive biomarker and provide information on modifiable risk factors driving health outcomes. On the other hand, there are several limitations to implementing PRSs in clinical practice, such as biased sensitivity for the ethnic background of PRS calculation and geographical differences even in the same population groups. Also, it remains unclear which method is the most suitable for the prediction with high accuracy among numerous PRS methods developed so far. Although further improvements of its comprehensiveness and generalizability will be needed for its clinical implementation in the future, PRS will be a powerful tool for therapeutic interventions and lifestyle recommendations in a wide range of diseases. Thus, it may ultimately improve the health of an entire population in the future.</p>","PeriodicalId":13588,"journal":{"name":"Inflammation and Regeneration","volume":"41 1","pages":"18"},"PeriodicalIF":8.1,"publicationDate":"2021-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s41232-021-00172-9","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39241804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-06-15DOI: 10.1186/s41232-021-00167-6
Yuko Ota, Masataka Kuwana
Systemic sclerosis (SSc) is a complex disease, in which an interaction of genetic and environmental factors plays an important role in its development and pathogenesis. A number of genetic studies, including candidate gene analysis and genome-wide association study, have found that the associated genetic variants are mainly localized in noncoding regions in the expression quantitative trait locus and influence corresponding gene expression. The gene variants identified as a risk for SSc susceptibility include those associated with innate immunity, adaptive immune response, and cell death, while there are only few SSc-associated genes involved in the fibrotic process or vascular homeostasis. Human leukocyte antigen class II genes are associated with SSc-related autoantibodies rather than SSc itself. Since the pathways between the associated genotype and phenotype are still poorly understood, further investigations using multi-omics technologies are necessary to characterize the complex molecular architecture of SSc, identify biomarkers useful to predict future outcomes and treatment responses, and discover effective drug targets.
{"title":"Updates on genetics in systemic sclerosis.","authors":"Yuko Ota, Masataka Kuwana","doi":"10.1186/s41232-021-00167-6","DOIUrl":"https://doi.org/10.1186/s41232-021-00167-6","url":null,"abstract":"<p><p>Systemic sclerosis (SSc) is a complex disease, in which an interaction of genetic and environmental factors plays an important role in its development and pathogenesis. A number of genetic studies, including candidate gene analysis and genome-wide association study, have found that the associated genetic variants are mainly localized in noncoding regions in the expression quantitative trait locus and influence corresponding gene expression. The gene variants identified as a risk for SSc susceptibility include those associated with innate immunity, adaptive immune response, and cell death, while there are only few SSc-associated genes involved in the fibrotic process or vascular homeostasis. Human leukocyte antigen class II genes are associated with SSc-related autoantibodies rather than SSc itself. Since the pathways between the associated genotype and phenotype are still poorly understood, further investigations using multi-omics technologies are necessary to characterize the complex molecular architecture of SSc, identify biomarkers useful to predict future outcomes and treatment responses, and discover effective drug targets.</p>","PeriodicalId":13588,"journal":{"name":"Inflammation and Regeneration","volume":"41 1","pages":"17"},"PeriodicalIF":8.1,"publicationDate":"2021-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s41232-021-00167-6","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39234012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-06-03DOI: 10.1186/s41232-021-00166-7
Hideki Amano, Yoshio Matsui, Ko Hatanaka, Kanako Hosono, Yoshiya Ito
Vascular endothelial growth factor (VEGF) is not only an important factor for angiogenesis but also lung development and homeostasis. VEGF-A binds three tyrosine kinase (TK) receptors VEGFR1-3. Idiopathic pulmonary fibrosis (IPF) is one of the poor prognoses of lung diseases. The relationship of VEGF and IPF remains to be clarified. Treatment with nintedanib used for the treatment of IPF reduced fibroblast proliferation, inhibited TK receptors, platelet-derived growth factor receptor (PDGFR), fibroblast growth factor receptor (FGFR), and VEGFR. Because the effect of that treatment is still not satisfactory, the emergence of new therapeutic agents is needed. This review describes the enhancement of pulmonary fibrosis by VEGFR1-TK signal and suggests that the blocking of the VEGFR1-TK signal may be useful for the treatment of pulmonary fibrosis.
{"title":"VEGFR1-tyrosine kinase signaling in pulmonary fibrosis.","authors":"Hideki Amano, Yoshio Matsui, Ko Hatanaka, Kanako Hosono, Yoshiya Ito","doi":"10.1186/s41232-021-00166-7","DOIUrl":"https://doi.org/10.1186/s41232-021-00166-7","url":null,"abstract":"<p><p>Vascular endothelial growth factor (VEGF) is not only an important factor for angiogenesis but also lung development and homeostasis. VEGF-A binds three tyrosine kinase (TK) receptors VEGFR1-3. Idiopathic pulmonary fibrosis (IPF) is one of the poor prognoses of lung diseases. The relationship of VEGF and IPF remains to be clarified. Treatment with nintedanib used for the treatment of IPF reduced fibroblast proliferation, inhibited TK receptors, platelet-derived growth factor receptor (PDGFR), fibroblast growth factor receptor (FGFR), and VEGFR. Because the effect of that treatment is still not satisfactory, the emergence of new therapeutic agents is needed. This review describes the enhancement of pulmonary fibrosis by VEGFR1-TK signal and suggests that the blocking of the VEGFR1-TK signal may be useful for the treatment of pulmonary fibrosis.</p>","PeriodicalId":13588,"journal":{"name":"Inflammation and Regeneration","volume":"41 1","pages":"16"},"PeriodicalIF":8.1,"publicationDate":"2021-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s41232-021-00166-7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39058918","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-05-07DOI: 10.1186/s41232-021-00165-8
Yoshitaka Kase, Hideyuki Okano
Since the worldwide outbreak of coronavirus disease 2019 (COVID-19) in 2020, various research reports and case reports have been published. It has been found that COVID-19 causes not only respiratory disorders but also thrombosis and gastrointestinal disorders, central nervous system (CNS) disorders, and peripheral neuropathy. Compared to other disorders, there are low number of research reports and low number of summaries on COVID-19-related neural disorders. Therefore, focusing on neural disorders, we outline both basic research and clinical manifestations of COVID-19-related neural disorders.
{"title":"Neurological pathogenesis of SARS-CoV-2 (COVID-19): from virological features to clinical symptoms.","authors":"Yoshitaka Kase, Hideyuki Okano","doi":"10.1186/s41232-021-00165-8","DOIUrl":"10.1186/s41232-021-00165-8","url":null,"abstract":"<p><p>Since the worldwide outbreak of coronavirus disease 2019 (COVID-19) in 2020, various research reports and case reports have been published. It has been found that COVID-19 causes not only respiratory disorders but also thrombosis and gastrointestinal disorders, central nervous system (CNS) disorders, and peripheral neuropathy. Compared to other disorders, there are low number of research reports and low number of summaries on COVID-19-related neural disorders. Therefore, focusing on neural disorders, we outline both basic research and clinical manifestations of COVID-19-related neural disorders.</p>","PeriodicalId":13588,"journal":{"name":"Inflammation and Regeneration","volume":"41 1","pages":"15"},"PeriodicalIF":5.0,"publicationDate":"2021-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8103065/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38961125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-05-03DOI: 10.1186/s41232-021-00164-9
He Hao, Shingo Nakayamada, Yoshiya Tanaka
T follicular helper cells participate in stimulating germinal center (GC) formation and supporting B cell differentiation and autoantibody production. However, T follicular regulatory (Tfr) cells suppress B cell activation. Since changes in the number and functions of Tfr cells lead to dysregulated GC reaction and autoantibody response, targeting Tfr cells may benefit the treatment of autoimmune diseases. Differentiation of Tfr cells is a multistage and multifactorial process with various positive and negative regulators. Therefore, understanding the signals regulating Tfr cell generation is crucial for the development of targeted therapies. In this review, we discuss recent studies that have elucidated the roles of Tfr cells in autoimmune diseases and investigated the modulators of Tfr cell differentiation. Additionally, potential immunotherapies targeting Tfr cells are highlighted.
{"title":"Differentiation, functions, and roles of T follicular regulatory cells in autoimmune diseases.","authors":"He Hao, Shingo Nakayamada, Yoshiya Tanaka","doi":"10.1186/s41232-021-00164-9","DOIUrl":"https://doi.org/10.1186/s41232-021-00164-9","url":null,"abstract":"<p><p>T follicular helper cells participate in stimulating germinal center (GC) formation and supporting B cell differentiation and autoantibody production. However, T follicular regulatory (Tfr) cells suppress B cell activation. Since changes in the number and functions of Tfr cells lead to dysregulated GC reaction and autoantibody response, targeting Tfr cells may benefit the treatment of autoimmune diseases. Differentiation of Tfr cells is a multistage and multifactorial process with various positive and negative regulators. Therefore, understanding the signals regulating Tfr cell generation is crucial for the development of targeted therapies. In this review, we discuss recent studies that have elucidated the roles of Tfr cells in autoimmune diseases and investigated the modulators of Tfr cell differentiation. Additionally, potential immunotherapies targeting Tfr cells are highlighted.</p>","PeriodicalId":13588,"journal":{"name":"Inflammation and Regeneration","volume":"41 1","pages":"14"},"PeriodicalIF":8.1,"publicationDate":"2021-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s41232-021-00164-9","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38858762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Silicone tube (ST) conduits have been accepted as a therapeutic alternative to direct nerve suturing in the treatment of nerve injuries; however, the search for optimal adjuncts to maximize the outcomes is still ongoing. Frankincense (Fr) and graphene oxide (GO) have both been cited as neuroregenerative compounds in the literature. This study assesses the efficacy of these materials using a ST conduit in a rat facial nerve motor neuron axotomy model, distal to the stylomastoid foramen.
Methods: Ammonia-functionalized graphene oxide (NH2-GO) and/or Fr extract were embedded in a collagen-chitosan hydrogel and were injected inside a ST. The ST was inserted in the gap between the axotomized nerve stumps. Return of function in eye closure, blinking reflex, and vibrissae movements were assessed and compared to control groups through 30 days following axotomy. To assess the histological properties of regenerated nerves, biopsies were harvested distal to the axotomy site and were visualized through light and fluorescence microscopy using LFB and anti-MBP marker, respectively.
Results: There was no significant difference in behavioral test results between groups. Histological analysis of the nerve sections revealed increased number of regenerating axons and mean axon diameter in NH2-GO group and decreased myelin surface area in Fr group. Using both NH2-GO and Fr resulted in increased number of regenerated axons and myelin thickness compared to the hydrogel group.
Conclusions: The findings suggest a synergistic effect of the substances above in axon regrowth, notably in myelin regeneration, where Fr supposedly decreases myelin synthesis.
{"title":"Facial nerve regeneration using silicone conduits filled with ammonia-functionalized graphene oxide and frankincense-embedded hydrogel.","authors":"Sepehr Aghajanian, Aliasghar Taghi Doulabi, Masoume Akhbari, Alireza Shams","doi":"10.1186/s41232-021-00162-x","DOIUrl":"https://doi.org/10.1186/s41232-021-00162-x","url":null,"abstract":"<p><strong>Background: </strong>Silicone tube (ST) conduits have been accepted as a therapeutic alternative to direct nerve suturing in the treatment of nerve injuries; however, the search for optimal adjuncts to maximize the outcomes is still ongoing. Frankincense (Fr) and graphene oxide (GO) have both been cited as neuroregenerative compounds in the literature. This study assesses the efficacy of these materials using a ST conduit in a rat facial nerve motor neuron axotomy model, distal to the stylomastoid foramen.</p><p><strong>Methods: </strong>Ammonia-functionalized graphene oxide (NH2-GO) and/or Fr extract were embedded in a collagen-chitosan hydrogel and were injected inside a ST. The ST was inserted in the gap between the axotomized nerve stumps. Return of function in eye closure, blinking reflex, and vibrissae movements were assessed and compared to control groups through 30 days following axotomy. To assess the histological properties of regenerated nerves, biopsies were harvested distal to the axotomy site and were visualized through light and fluorescence microscopy using LFB and anti-MBP marker, respectively.</p><p><strong>Results: </strong>There was no significant difference in behavioral test results between groups. Histological analysis of the nerve sections revealed increased number of regenerating axons and mean axon diameter in NH2-GO group and decreased myelin surface area in Fr group. Using both NH2-GO and Fr resulted in increased number of regenerated axons and myelin thickness compared to the hydrogel group.</p><p><strong>Conclusions: </strong>The findings suggest a synergistic effect of the substances above in axon regrowth, notably in myelin regeneration, where Fr supposedly decreases myelin synthesis.</p>","PeriodicalId":13588,"journal":{"name":"Inflammation and Regeneration","volume":"41 1","pages":"13"},"PeriodicalIF":8.1,"publicationDate":"2021-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s41232-021-00162-x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38832106","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Extracellular vesicles (EVs) are known to be secreted by various cells. In particular, mesenchymal stem cell (MSC)-derived EVs (MSC-EVs) have tissue repair capacity and anti-inflammatory properties. Dental pulp stem cells (DPSCs), which are MSCs isolated from pulp tissue, are less invasive to the body than other MSCs and can be collected from young individuals. In this study, we investigated the efficacy of EVs secreted by DPSCs (DPSC-EVs) for bone formation.
Methods: DPSC-EVs were isolated from the cell culture medium of DPSCs. DPSC-EVs were unilaterally injected along with collagen (COL), beta-tricalcium phosphate (β-TCP) or hydroxyapatite (HA) into rat calvarial bone defects. The effects of DPSC-EVs were analyzed by micro-computed tomography (micro-CT) and histological observation.
Results: Micro-CT showed that administration of DPSC-EVs with the abovementioned scaffolds resulted in bone formation in the periphery of the defects. DPSC-EVs/COL specifically resulted in bone formation in the center of the defects. Histological observation revealed that DPSC-EVs/COL promoted new bone formation. Administration of DPSC-EVs/COL had almost the same effect on the bone defect site as transplantation of DPSCs/COL.
Conclusions: These results suggest that DPSC-EVs may be effective tools for bone tissue regeneration.
背景:细胞外囊泡(EVs)是由多种细胞分泌的。特别是间充质干细胞(MSC)衍生的EVs (MSC-EVs)具有组织修复能力和抗炎特性。牙髓干细胞(DPSCs)是一种从牙髓组织中分离出来的间充质干细胞,与其他间充质干细胞相比,对身体的侵袭性较小,可以从年轻人身上采集。在这项研究中,我们研究了由dpsc分泌的EVs (DPSC-EVs)对骨形成的影响。方法:从dpsc细胞培养基中分离dpsc - ev。将DPSC-EVs与胶原(COL)、β-磷酸三钙(β-TCP)或羟基磷灰石(HA)一起单侧注入大鼠颅骨骨缺损。通过显微计算机断层扫描(micro-CT)和组织学观察分析dpsc - ev的作用。结果:Micro-CT显示,将dpsc - ev与上述支架一起使用可使缺损周围骨形成。dpsc - ev /COL特异性地导致缺损中心的骨形成。组织学观察显示DPSC-EVs/COL促进新骨形成。DPSCs - ev /COL对骨缺损部位的影响与DPSCs/COL移植几乎相同。结论:这些结果提示dpsc - ev可能是骨组织再生的有效工具。
{"title":"Efficacy of extracellular vesicles from dental pulp stem cells for bone regeneration in rat calvarial bone defects.","authors":"Yuka Imanishi, Masaki Hata, Ryohei Matsukawa, Atsushi Aoyagi, Maiko Omi, Makoto Mizutani, Keiko Naruse, Shogo Ozawa, Masaki Honda, Tatsuaki Matsubara, Jun Takebe","doi":"10.1186/s41232-021-00163-w","DOIUrl":"https://doi.org/10.1186/s41232-021-00163-w","url":null,"abstract":"<p><strong>Background: </strong>Extracellular vesicles (EVs) are known to be secreted by various cells. In particular, mesenchymal stem cell (MSC)-derived EVs (MSC-EVs) have tissue repair capacity and anti-inflammatory properties. Dental pulp stem cells (DPSCs), which are MSCs isolated from pulp tissue, are less invasive to the body than other MSCs and can be collected from young individuals. In this study, we investigated the efficacy of EVs secreted by DPSCs (DPSC-EVs) for bone formation.</p><p><strong>Methods: </strong>DPSC-EVs were isolated from the cell culture medium of DPSCs. DPSC-EVs were unilaterally injected along with collagen (COL), beta-tricalcium phosphate (β-TCP) or hydroxyapatite (HA) into rat calvarial bone defects. The effects of DPSC-EVs were analyzed by micro-computed tomography (micro-CT) and histological observation.</p><p><strong>Results: </strong>Micro-CT showed that administration of DPSC-EVs with the abovementioned scaffolds resulted in bone formation in the periphery of the defects. DPSC-EVs/COL specifically resulted in bone formation in the center of the defects. Histological observation revealed that DPSC-EVs/COL promoted new bone formation. Administration of DPSC-EVs/COL had almost the same effect on the bone defect site as transplantation of DPSCs/COL.</p><p><strong>Conclusions: </strong>These results suggest that DPSC-EVs may be effective tools for bone tissue regeneration.</p>","PeriodicalId":13588,"journal":{"name":"Inflammation and Regeneration","volume":"41 1","pages":"12"},"PeriodicalIF":8.1,"publicationDate":"2021-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s41232-021-00163-w","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25591963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-04-09DOI: 10.1186/s41232-021-00161-y
Masahiro Nakano, Yukiko Iwasaki, Keishi Fujio
The management of systemic lupus erythematosus (SLE) remains challenging for clinicians because of the clinical heterogeneity of this disease. In attempts to identify useful biomarkers for the diagnosis of and treatment strategies for SLE, previous microarray and RNA sequencing studies have demonstrated several disease-relevant signatures in SLE. Of these, the interferon (IFN) signature is complex, involving IFNβ- and IFNγ-response genes in addition to IFNα-response genes. Some studies revealed that myeloid lineage/neutrophil and plasma cell signatures as well as the IFN signature were correlated with disease activity, lupus nephritis, and complications of pregnancy, although some of these findings remain controversial. Cell-type-specific gene expression analysis revealed the importance of an exhaustion signature in CD8+ T cells for SLE outcome. Recent single-cell RNA sequencing analyses of SLE blood and tissues demonstrated molecular heterogeneity and identified several distinct subpopulations as key players in SLE pathogenesis. Further studies are required to identify novel treatment targets and determine precise patient stratification in SLE. In this review, we discuss the findings and limitations of SLE transcriptomic studies.
{"title":"Transcriptomic studies of systemic lupus erythematosus.","authors":"Masahiro Nakano, Yukiko Iwasaki, Keishi Fujio","doi":"10.1186/s41232-021-00161-y","DOIUrl":"10.1186/s41232-021-00161-y","url":null,"abstract":"<p><p>The management of systemic lupus erythematosus (SLE) remains challenging for clinicians because of the clinical heterogeneity of this disease. In attempts to identify useful biomarkers for the diagnosis of and treatment strategies for SLE, previous microarray and RNA sequencing studies have demonstrated several disease-relevant signatures in SLE. Of these, the interferon (IFN) signature is complex, involving IFNβ- and IFNγ-response genes in addition to IFNα-response genes. Some studies revealed that myeloid lineage/neutrophil and plasma cell signatures as well as the IFN signature were correlated with disease activity, lupus nephritis, and complications of pregnancy, although some of these findings remain controversial. Cell-type-specific gene expression analysis revealed the importance of an exhaustion signature in CD8<sup>+</sup> T cells for SLE outcome. Recent single-cell RNA sequencing analyses of SLE blood and tissues demonstrated molecular heterogeneity and identified several distinct subpopulations as key players in SLE pathogenesis. Further studies are required to identify novel treatment targets and determine precise patient stratification in SLE. In this review, we discuss the findings and limitations of SLE transcriptomic studies.</p>","PeriodicalId":13588,"journal":{"name":"Inflammation and Regeneration","volume":"41 1","pages":"11"},"PeriodicalIF":8.1,"publicationDate":"2021-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8033719/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25575473","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-03-29DOI: 10.1186/s41232-021-00160-z
Daiju Fukuda, Masataka Sata
{"title":"Frontiers of inflammatory disease research: inflammation in cardiovascular-cerebral diseases.","authors":"Daiju Fukuda, Masataka Sata","doi":"10.1186/s41232-021-00160-z","DOIUrl":"https://doi.org/10.1186/s41232-021-00160-z","url":null,"abstract":"","PeriodicalId":13588,"journal":{"name":"Inflammation and Regeneration","volume":"41 1","pages":"10"},"PeriodicalIF":8.1,"publicationDate":"2021-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s41232-021-00160-z","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25528597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Primary immunodeficiency (PID) is a genetic disorder with a defect of one of the important components of our immune system. Classical PID has been recognized as a disorder with loss of function of the immune system. Recent studies have unveiled disorders with immune dysfunction with autoimmunity, autoinflammation, allergy, or predisposition to malignancy. Some of them were caused by an augmented immune function or a defect in immune regulation. With this background, the term inborn errors of immunity (IEI) is now used to refer to PID in the International Union of Immunological Societies (IUIS) classification. More than 400 responsible genes have been identified in patients with IEI so far, and importantly, many of them identified lately were caused by a heterologous mutation. Moreover, the onset is not necessarily in childhood, and we started seeing more and more IEI patients diagnosed in adulthood in the clinical settings. Recent advances in genetic analysis, including whole-exome analysis, whole-genome analysis, and RNA-seq have contributed to the identification of the disease-causing gene mutation. We also started to find heterogeneity of phenotype even in the patients with the same mutation in the same family, leading us to wonder if modifier gene or epigenetic modification is involved in the pathogenesis. In contrast, we accumulated many cases suggesting genetic heterogeneity is associated with phenotypic homogeneity. It has thus become difficult to deduce a responsible gene only from the phenotype in a certain type of IEI. Current curative therapy for IEI includes hematopoietic cell transplantation and gene therapy. Other curative therapeutic modalities have been long waited and are to be introduced in the future. These include a small molecule that inhibits the gain-of-function of the molecule- and genome-editing technology. Research on IEI will surely lead to a better understanding of other immune-related disorders including rheumatic diseases and atopic disorders.
{"title":"Inborn errors of immunity-recent advances in research on the pathogenesis.","authors":"Motoi Yamashita, Kento Inoue, Tsubasa Okano, Tomohiro Morio","doi":"10.1186/s41232-021-00159-6","DOIUrl":"https://doi.org/10.1186/s41232-021-00159-6","url":null,"abstract":"<p><p>Primary immunodeficiency (PID) is a genetic disorder with a defect of one of the important components of our immune system. Classical PID has been recognized as a disorder with loss of function of the immune system. Recent studies have unveiled disorders with immune dysfunction with autoimmunity, autoinflammation, allergy, or predisposition to malignancy. Some of them were caused by an augmented immune function or a defect in immune regulation. With this background, the term inborn errors of immunity (IEI) is now used to refer to PID in the International Union of Immunological Societies (IUIS) classification. More than 400 responsible genes have been identified in patients with IEI so far, and importantly, many of them identified lately were caused by a heterologous mutation. Moreover, the onset is not necessarily in childhood, and we started seeing more and more IEI patients diagnosed in adulthood in the clinical settings. Recent advances in genetic analysis, including whole-exome analysis, whole-genome analysis, and RNA-seq have contributed to the identification of the disease-causing gene mutation. We also started to find heterogeneity of phenotype even in the patients with the same mutation in the same family, leading us to wonder if modifier gene or epigenetic modification is involved in the pathogenesis. In contrast, we accumulated many cases suggesting genetic heterogeneity is associated with phenotypic homogeneity. It has thus become difficult to deduce a responsible gene only from the phenotype in a certain type of IEI. Current curative therapy for IEI includes hematopoietic cell transplantation and gene therapy. Other curative therapeutic modalities have been long waited and are to be introduced in the future. These include a small molecule that inhibits the gain-of-function of the molecule- and genome-editing technology. Research on IEI will surely lead to a better understanding of other immune-related disorders including rheumatic diseases and atopic disorders.</p>","PeriodicalId":13588,"journal":{"name":"Inflammation and Regeneration","volume":"41 1","pages":"9"},"PeriodicalIF":8.1,"publicationDate":"2021-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s41232-021-00159-6","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25518026","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}