Immunoglobulin A (IgA) is important in local immunity and is also abundant in the blood. This study aimed to evaluate the effects of serum IgA on cultured lung microvascular endothelial cells (HMVEC-Ls), which are involved in the pathogenesis of inflammatory lung diseases. Serum IgA induced adhesion molecules and inflammatory cytokine production from HMVEC-Ls, and enhanced adhesion of peripheral blood mononuclear cells to HMVEC-Ls. In contrast, migration, proliferation, and tube formation of HMVEC-Ls were significantly suppressed by serum IgA. Experiments with siRNAs and western blotting revealed that two known IgA receptors, β1,4-galactosyltransferase 1 (b4GALT1) and asialoglycoprotein receptor 1 (ASGR1), and mitogen-activated protein kinase and nuclear factor-kappa B pathways were partly involved in serum IgA-induced cytokine production by HMVEC-Ls. Collectively, serum IgA enhanced cytokine production and adhesiveness of HMVEC-L, with b4GALT1 and ASGR1 partially being involved, and suppressed angiogenesis. Thus, serum IgA may be targeted to treat inflammatory lung diseases.
{"title":"Serum IgA augments adhesiveness of cultured lung microvascular endothelial cells and suppresses angiogenesis","authors":"Kazufumi Takada , Maho Suzukawa , Sayaka Igarashi , Yuuki Uehara , Shizuka Watanabe , Sahoko Imoto , Masaki Ishii , Yoshiteru Morio , Hirotoshi Matsui , Masahiro Akishita , Ken Ohta","doi":"10.1016/j.cellimm.2023.104769","DOIUrl":"10.1016/j.cellimm.2023.104769","url":null,"abstract":"<div><p>Immunoglobulin A (IgA) is important in local immunity and is also abundant in the blood. This study aimed to evaluate the effects of serum IgA on cultured lung microvascular endothelial cells (HMVEC-Ls), which are involved in the pathogenesis of inflammatory lung diseases. Serum IgA induced adhesion molecules and inflammatory cytokine production from HMVEC-Ls, and enhanced adhesion of peripheral blood mononuclear cells to HMVEC-Ls. In contrast, migration, proliferation, and tube formation of HMVEC-Ls were significantly suppressed by serum IgA. Experiments with siRNAs and western blotting revealed that two known IgA receptors, β1,4-galactosyltransferase 1 (b4GALT1) and asialoglycoprotein receptor 1 (ASGR1), and mitogen-activated protein kinase and nuclear factor-kappa B pathways were partly involved in serum IgA-induced cytokine production by HMVEC-Ls. Collectively, serum IgA enhanced cytokine production and adhesiveness of HMVEC-L, with b4GALT1 and ASGR1 partially being involved, and suppressed angiogenesis. Thus, serum IgA may be targeted to treat inflammatory lung diseases.</p></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2023-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41115511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-01DOI: 10.1016/j.cellimm.2023.104758
Shalini Roy , Anand K Gupta , Madhurima Banerjee , Pijush K. Das , Anindita Ukil
The anti-inflammatory role of the programmed death-1 receptor (PD-1) is well appreciated. However, the mechanism of how PD-1 signaling inhibits the pro-inflammatory cytokine responses in macrophages, which is further exploited by Leishmania to foster their intracellular survival, was unknown. We found that among three major MAP kinases regulating immune activation, PD-1 signaling decreased only JNK phosphorylation without perturbing p38 and ERK. Inflammatory transcription factor STAT1 was also inhibited by PD-1. Association studies documented that SHP, the downstream phosphatase of PD-1, is directly responsible for the decreased phosphorylation of JNK and STAT1. JNK and STAT1 deactivation led to Elk-1/c-Fos inhibition, which significantly decreased IL-12 and TNF-α levels. Further investigation revealed c-Fos deactivation ultimately rendered transcription factor AP1 inactive and facilitating parasite-favorable anti-inflammatory environment.
{"title":"PD-1 negatively tunes macrophage immune activation by turning off JNK and STAT1 signaling: Exploited by Leishmania for its intra-macrophage survival","authors":"Shalini Roy , Anand K Gupta , Madhurima Banerjee , Pijush K. Das , Anindita Ukil","doi":"10.1016/j.cellimm.2023.104758","DOIUrl":"10.1016/j.cellimm.2023.104758","url":null,"abstract":"<div><p>The anti-inflammatory role of the programmed death-1 receptor (PD-1) is well appreciated. However, the mechanism of how PD-1 signaling inhibits the pro-inflammatory cytokine responses in macrophages, which is further exploited by <em>Leishmania</em> to foster their intracellular survival, was unknown. We found that among three major MAP kinases regulating immune activation, PD-1 signaling decreased only JNK phosphorylation without perturbing p38 and ERK. Inflammatory transcription factor STAT1 was also inhibited by PD-1. Association studies documented that SHP, the downstream phosphatase of PD-1, is directly responsible for the decreased phosphorylation of JNK and STAT1. JNK and STAT1 deactivation led to Elk-1/c-Fos inhibition, which significantly decreased IL-12 and TNF-α levels. Further investigation revealed c-Fos deactivation ultimately rendered transcription factor AP1 inactive and facilitating parasite-favorable anti-inflammatory environment.</p></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10314827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-01DOI: 10.1016/j.cellimm.2023.104756
Eddie A. James
{"title":"Editorial: Processing, presentation, and recognition of T cell determinants: From molecular insights to clinical applications","authors":"Eddie A. James","doi":"10.1016/j.cellimm.2023.104756","DOIUrl":"10.1016/j.cellimm.2023.104756","url":null,"abstract":"","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10260836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-01DOI: 10.1016/j.cellimm.2023.104753
Sun Lina , Han Ya'nan , Yang Ying , Wang Fengfan , Hou Xin , Ren Xiaoxia , Fang Ying
Loss-of-function of protein A20, encoded by TNFAIP3, leads to an early-onset haploinsufficiency of A20 (HA20). This study reports one Chinese child with HA20 and explores the genetic etiology of TNFAIP3 variant. The patient exhibited transient recurrent episodes of fever, intermittent signs of arthritis, gastrointestinal symptoms and multiple colonic ulcers. Laboratory tests revealed elevated inflammatory indicators and mild to moderate anemia. Genetic analysis identified a heterozygous de novo variant in his TNFAIP3 gene (c.740C>T, p. P247L), which had never been reported before. The novel missense variation was validated to be pathogenic through causing insufficient expression of A20, over-activation of NF-κB signaling pathway and elevated levels of proinflammatory cytokines in response to stimulation by lipopolysaccharide. A combination of oral corticosteroids, TNF-α inhibitors and thalidomide freed him from symptoms and abnormal inflammatory indicators. Furthermore, continual improvement of the patient's condition was observed during a follow-up period of five months. We demonstrate a case with a de novo missense variant resulting in a loss-of-function of TNFAIP3, which expands the clinical spectrum of HA20. Cytokine antagonists and immunosuppressants may be effective drugs.
{"title":"Haploinsufficiency of A20 caused by a novel pathogenic missense variant of TNFAIP3 and successfully treated with anti-TNF and immunosuppressive therapies","authors":"Sun Lina , Han Ya'nan , Yang Ying , Wang Fengfan , Hou Xin , Ren Xiaoxia , Fang Ying","doi":"10.1016/j.cellimm.2023.104753","DOIUrl":"10.1016/j.cellimm.2023.104753","url":null,"abstract":"<div><p>Loss-of-function of protein A20, encoded by <em>TNFAIP3</em>, leads to an early-onset haploinsufficiency of A20 (HA20). This study reports one Chinese child with HA20 and explores the genetic etiology of <em>TNFAIP3</em> variant. The patient exhibited transient recurrent episodes of fever, intermittent signs of arthritis, gastrointestinal symptoms and multiple colonic ulcers. Laboratory tests revealed elevated inflammatory indicators and mild to moderate anemia. Genetic analysis identified a heterozygous <em>de novo</em> variant in his <em>TNFAIP3</em> gene (c.740C>T, p. P247L), which had never been reported before. The novel missense variation was validated to be pathogenic through causing insufficient expression of A20, over-activation of NF-κB signaling pathway and elevated levels of proinflammatory cytokines in response to stimulation by lipopolysaccharide. A combination of oral corticosteroids, TNF-α inhibitors and thalidomide freed him from symptoms and abnormal inflammatory indicators. Furthermore, continual improvement of the patient's condition was observed during a follow-up period of five months. We demonstrate a case with a <em>de novo</em> missense variant resulting in a loss-of-function of <em>TNFAIP3</em>, which expands the clinical spectrum of HA20. Cytokine antagonists and immunosuppressants may be effective drugs.</p></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10260807","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-01DOI: 10.1016/j.cellimm.2023.104759
Lele Cui , Xiaofeng Qin , Tingting Fu , Chenduo Li , Dan Wang , Yue Hu , Yan Li , Yan Chen , Ye Cui , Jingjing Wang , Huihui Yuan , Zhe Lv , Jie Liu , Damo Xu , Rongfei Wei , Sun Ying , Wei Wang
Background
Asthma is a common chronic respiratory disease characterized by airways inflammation, hyperresponsiveness and remodeling. IL-37, an anti-inflammatory cytokine, consists of five splice isoforms, that is, a-e. Although it has been previously shown that recombinant human IL-37b is able to inhibit airway inflammation and hyperresponsiveness in animal models of asthma, the effects and difference of other IL-37 isoforms, such as IL-37a on features of asthma are unknown.
Methods
Animal models of chronic asthma were established using IL-37a and IL-37b transgenic mice with C57BL/6J background and wild-type (WT) mice sensitized and nasally challenged with ovalbumin (OVA). Airway hyperresponsiveness was measured using FlexiVent apparatus, while histological and immunohistological stainings were employed to measure airways inflammation and remodeling indexes, including goblet cell metaplasia, mucus production, deposition of collagen, hypertrophy of airway smooth muscles and pulmonary angiogenesis.
Results
Compared to WT mice, both IL-37a and IL-37b transgenic mice had significant reduced airway hyperresponsiveness and the declined total numbers of inflammatory cells, predominant eosinophils into airways and lung tissues. Furthermore, all features of airways remodeling, including degrees of mucus expression, collagen deposition, hypertrophy of smooth muscles, thickness of airways and neovascularization markedly decreased in IL-37 transgenic mice compared with OVA-treated WT mice.
Conclusion
Our data suggest that both IL-37a and IL-37b isoforms are able to not only ameliorate airways inflammation and airways hyperresponsiveness, but also greatly reduce airways structural changes of animal models of chronic asthma.
{"title":"Attenuated airways inflammation and remodeling in IL-37a and IL-37b transgenic mice with an ovalbumin-induced chronic asthma","authors":"Lele Cui , Xiaofeng Qin , Tingting Fu , Chenduo Li , Dan Wang , Yue Hu , Yan Li , Yan Chen , Ye Cui , Jingjing Wang , Huihui Yuan , Zhe Lv , Jie Liu , Damo Xu , Rongfei Wei , Sun Ying , Wei Wang","doi":"10.1016/j.cellimm.2023.104759","DOIUrl":"10.1016/j.cellimm.2023.104759","url":null,"abstract":"<div><h3>Background</h3><p>Asthma is a common chronic respiratory disease characterized by airways inflammation, hyperresponsiveness and remodeling. IL-37, an anti-inflammatory cytokine, consists of five splice isoforms, that is, a-e. Although it has been previously shown that recombinant human IL-37b is able to inhibit airway inflammation and hyperresponsiveness in animal models of asthma, the effects and difference of other IL-37 isoforms, such as IL-37a on features of asthma are unknown.</p></div><div><h3>Methods</h3><p>Animal models of chronic asthma were established using IL-37a and IL-37b transgenic mice with C57BL/6J background and wild-type (WT) mice sensitized and nasally challenged with ovalbumin (OVA). Airway hyperresponsiveness was measured using FlexiVent apparatus, while histological and immunohistological stainings were employed to measure airways inflammation and remodeling indexes, including goblet cell metaplasia, mucus production, deposition of collagen, hypertrophy of airway smooth muscles and pulmonary angiogenesis.</p></div><div><h3>Results</h3><p>Compared to WT mice, both IL-37a and IL-37b transgenic mice had significant reduced airway hyperresponsiveness and the declined total numbers of inflammatory cells, predominant eosinophils into airways and lung tissues. Furthermore, all features of airways remodeling, including degrees of mucus expression, collagen deposition, hypertrophy of smooth muscles, thickness of airways and neovascularization markedly decreased in IL-37 transgenic mice compared with OVA-treated WT mice.</p></div><div><h3>Conclusion</h3><p>Our data suggest that both IL-37a and IL-37b isoforms are able to not only ameliorate airways inflammation and airways hyperresponsiveness, but also greatly reduce airways structural changes of animal models of chronic asthma.</p></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10261900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-01DOI: 10.1016/j.cellimm.2023.104752
Qoyama Noel Baito, Halmat M. Jaafar, Talar Ahmad Merza Mohammad
Rheumatoid Arthritis (RA) is a common autoimmune disease recognized by hyperplasia of synoviocytes and chronic joint inflammation. Activation of fibroblast-like synoviocytes (FLSs) is one of the main features of RA which can trigger inflammation leading to articular cartilage and joint destruction. Aberrant activation of NF-κB signaling cascade was found to be responsible for the high proliferation and defective apoptosis of FLSs and subsequent inflammation in RA. Piperine is a principal constituent of piper species frequently used as antitumor and anti-inflammatory natural compound. In this study we aimed to assess the anti-inflammatory effect of piperine on RA-FLS through NF-κB inhibition.
FLSs were isolated from 68 RA patients and 30 healthy controls and were exposed to piperine. The main assays were MTT assay, flow cytometric analysis, PI staining, reverse transcription-PCR (RT-PCR), and ELISA.
Results showed that piperine can induce the apoptosis and reduce the proliferation of RA-FLSs in vitro. Moreover, piperine directly reduced the phosphorylation of NF-kB and the expression of NF-κB target genes related to RA-FLSs proliferation (c-Myc and Cycline D1), apoptosis inhibition (Bcl2 and Bcl-xl) and inflammation (COX2, IL-1β, TNF-α,IL-6, CCL5 and CXCL10) while increasing the expression of apoptosis related ones (Bax) in vitro. Piperine also reduced the protein levels of cytokines and chemokines secreted by FLSs as a result of NF-κB inhibition.
In conclusion, our results provide evidence for the anti-inflammatory capacity of piperine through inhibition of NF-κB pathway in FLSs proposing this compound as a suitable alternative for chemical treatment of RA.
{"title":"Piperine suppresses inflammatory fibroblast-like synoviocytes derived from rheumatoid arthritis patients Via NF-κB inhibition","authors":"Qoyama Noel Baito, Halmat M. Jaafar, Talar Ahmad Merza Mohammad","doi":"10.1016/j.cellimm.2023.104752","DOIUrl":"10.1016/j.cellimm.2023.104752","url":null,"abstract":"<div><p>Rheumatoid Arthritis (RA) is a common autoimmune disease recognized by hyperplasia of synoviocytes and chronic joint inflammation. Activation of fibroblast-like synoviocytes (FLSs) is one of the main features of RA which can trigger inflammation leading to articular cartilage and joint destruction. Aberrant activation of NF-κB signaling cascade was found to be responsible for the high proliferation and defective apoptosis of FLSs and subsequent inflammation in RA. Piperine is a principal constituent of piper species frequently used as antitumor and anti-inflammatory natural compound. In this study we aimed to assess the anti-inflammatory effect of piperine on RA-FLS through NF-κB inhibition.</p><p>FLSs were isolated from 68 RA patients and 30 healthy controls and were exposed to piperine. The main assays were MTT assay, flow cytometric analysis, PI staining, reverse transcription-PCR (RT-PCR), and ELISA.</p><p>Results showed that piperine can induce the apoptosis and reduce the proliferation of RA-FLSs in vitro. Moreover, piperine directly reduced the phosphorylation of NF-kB and the expression of NF-κB target genes related to RA-FLSs proliferation (c-Myc and Cycline D1), apoptosis inhibition (Bcl2 and Bcl-xl) and inflammation (COX2, IL-1β, TNF-α,IL-6, CCL5 and CXCL10) while increasing the expression of apoptosis related ones (Bax) in vitro. Piperine also reduced the protein levels of cytokines and chemokines secreted by FLSs as a result of NF-κB inhibition.</p><p>In conclusion, our results provide evidence for the anti-inflammatory capacity of piperine through inhibition of NF-κB pathway in FLSs proposing this compound as a suitable alternative for chemical treatment of RA.</p></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10314434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-01DOI: 10.1016/j.cellimm.2023.104743
Hanchen Yang , Qi Qin , Meng Wang , Yunsi Yin , Ruiyang Li , Yi Tang
The significance of peripheral immunity in the pathogenesis and progression of Alzheimer’s diseases (AD) has been recognized. Brain-infiltrated peripheral immune components transporting across the blood–brain barrier (BBB) may reshape the central immune environment. However, mechanisms of how these components open the BBB for AD occurrence and development and correlations between peripheral and central immunity have not been fully explored. Herein, we formulate a hypothesis whereby peripheral immunity as a critical factor allows AD to progress. Peripheral central immune cell crosstalk is associated with early AD pathology and related risk factors. The damaged BBB permits peripheral immune cells to enter the central immune system to deprive its immune privilege promoting the progression toward developing AD. This review summarizes the influences of risk factors on peripheral immunity, alongside their functions, highlighting the concept of peripheral and central immunity as an integrated system in AD pathogenesis, which has received scant attention before.
{"title":"Crosstalk between peripheral immunity and central nervous system in Alzheimer’s disease","authors":"Hanchen Yang , Qi Qin , Meng Wang , Yunsi Yin , Ruiyang Li , Yi Tang","doi":"10.1016/j.cellimm.2023.104743","DOIUrl":"10.1016/j.cellimm.2023.104743","url":null,"abstract":"<div><p>The significance of peripheral immunity in the pathogenesis and progression of Alzheimer’s diseases (AD) has been recognized. Brain-infiltrated peripheral immune components transporting across the blood–brain barrier (BBB) may reshape the central immune environment. However, mechanisms of how these components open the BBB for AD occurrence and development and correlations between peripheral and central immunity have not been fully explored. Herein, we formulate a hypothesis whereby peripheral immunity as a critical factor allows AD to progress. Peripheral central immune cell crosstalk is associated with early AD pathology and related risk factors. The damaged BBB permits peripheral immune cells to enter the central immune system to deprive its immune privilege promoting the progression toward developing AD. This review summarizes the influences of risk factors on peripheral immunity, alongside their functions, highlighting the concept of peripheral and central immunity as an integrated system in AD pathogenesis, which has received scant attention before.</p></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10256933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-01DOI: 10.1016/j.cellimm.2023.104751
Ashley Wagner , Syed Benazir Alam , Marianna Kulka
Mast cells initiate allergic inflammatory immune responses and play a role in disease by releasing various inflammatory and immunomodulatory mediators. Several mast cell-lines and primary cultured cells have been used as mast cell models with inconsistent results among research groups. Bone marrow-derived mast cells (BMMC) cultured from mouse bone marrow progenitor cells are often used as a representative model of mucosal mast cell behaviour, however their reported phenotype is variable due to inconsistent culture protocols. RBL-2H3 is a rat basophilic histamine-releasing cell line that has some characteristics of both mast cells and basophils but is not a true representation of either cell type. The murine mast cell line MC/9 is an IL-3-dependent mucosal mast cell model but has limited mast cell characteristics. In this study, we have compared the response of BMMC (derived from C57BL/6 male or female mice), two sources of RBL-2H3 (purchased directly from ATCC and a lab curated culture), and MC/9 (ATCC) at several critical stages to some common stimuli (IgE/Ag, A23187) and analyzed mast cell morphology, expression level of common mast cell surface markers (CD117 and FcεRI), protease expression, and function (growth kinetics, viability, ROS production, degranulation, cytokine release and FcεRI signaling). The objective of this study was to provide insight into the effects of culture conditions, biological sex, and age of the cells on variability among reported phenotypes and, to determine optimal conditions for activation of these cells. Our data show that factors that are often overlooked such as source, age and biological sex of mast cells play an integral role in phenotypic outcomes and may account for the reported variability in their function.
{"title":"The effects of age, origin, and biological sex on rodent mast cell (BMMC and MC/9) and basophil (RBL-2H3) phenotype and function","authors":"Ashley Wagner , Syed Benazir Alam , Marianna Kulka","doi":"10.1016/j.cellimm.2023.104751","DOIUrl":"10.1016/j.cellimm.2023.104751","url":null,"abstract":"<div><p>Mast cells initiate allergic inflammatory immune responses and play a role in disease by releasing various inflammatory and immunomodulatory mediators. Several mast cell-lines and primary cultured cells have been used as mast cell models with inconsistent results among research groups. Bone marrow-derived mast cells (BMMC) cultured from mouse bone marrow progenitor cells are often used as a representative model of mucosal mast cell behaviour, however their reported phenotype is variable due to inconsistent culture protocols. RBL-2H3 is a rat basophilic histamine-releasing cell line that has some characteristics of both mast cells and basophils but is not a true representation of either cell type. The murine mast cell line MC/9 is an IL-3-dependent mucosal mast cell model but has limited mast cell characteristics. In this study, we have compared the response of BMMC (derived from C57BL/6 male or female mice), two sources of RBL-2H3 (purchased directly from ATCC and a lab curated culture), and MC/9 (ATCC) at several critical stages to some common stimuli (IgE/Ag, A23187) and analyzed mast cell morphology, expression level of common mast cell surface markers (CD117 and FcεRI), protease expression, and function (growth kinetics, viability, ROS production, degranulation, cytokine release and FcεRI signaling). The objective of this study was to provide insight into the effects of culture conditions, biological sex, and age of the cells on variability among reported phenotypes and, to determine optimal conditions for activation of these cells. Our data show that factors that are often overlooked such as source, age and biological sex of mast cells play an integral role in phenotypic outcomes and may account for the reported variability in their function.</p></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10623908","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-01DOI: 10.1016/j.cellimm.2023.104742
John S.S. Butterfield , Xin Li , Sreevani Arisa , Kwang-Chul Kwon , Henry Daniell , Roland W. Herzog
Oral immunotherapies are being developed for various autoimmune diseases and allergies to suppress immune responses in an antigen-specific manner. Previous studies have shown that anti-drug antibody (inhibitor) formation in protein replacement therapy for the inherited bleeding disorder hemophilia can be prevented by repeated oral delivery of coagulation factor antigens bioencapsulated in transplastomic lettuce cells. Here, we find that this approach substantially reduces antibody development against factor VIII in hemophilia A mice treated with adeno-associated viral gene transfer. We propose that the concept of oral tolerance can be applied to prevent immune responses against therapeutic transgene products expressed in gene therapy.
{"title":"Potential role for oral tolerance in gene therapy","authors":"John S.S. Butterfield , Xin Li , Sreevani Arisa , Kwang-Chul Kwon , Henry Daniell , Roland W. Herzog","doi":"10.1016/j.cellimm.2023.104742","DOIUrl":"10.1016/j.cellimm.2023.104742","url":null,"abstract":"<div><p>Oral immunotherapies are being developed for various autoimmune diseases and allergies to suppress immune responses in an antigen-specific manner. Previous studies have shown that anti-drug antibody (inhibitor) formation in protein replacement therapy for the inherited bleeding disorder hemophilia can be prevented by repeated oral delivery of coagulation factor antigens bioencapsulated in transplastomic lettuce cells. Here, we find that this approach substantially reduces antibody development against factor VIII in hemophilia A mice treated with adeno-associated viral gene transfer. We propose that the concept of oral tolerance can be applied to prevent immune responses against therapeutic transgene products expressed in gene therapy.</p></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10529677/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10261876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
SIRPα is a transmembrane protein that binds the protein tyrosine phosphatases SHP-1 and SHP-2 through its cytoplasmic region and is abundantly expressed on monocytes, dendritic cells, and macrophages. Studies recently showed that SIRPα is essential for priming of CD4 + T cells by DCs and for development of Th17 cell-mediated autoimmune diseases. We have now further evaluated the importance of SIRPα and that of its ligand CD47 in primary immune thrombocytopenia (ITP). In this study, we show that there was a low expression state of SIRPα on the surface of monocytes. Treatment of cells culture from ITP patients with a mAb to SIRPα that blocks the binding of SIRPα to CD47 downregulated the ITP response. The abilities of monocytes from ITP patients to stimulate an allogenic MLR were reduced. The proliferation of, and production of IL-2, by CD4 + T cells from ITP patients were inhibited, the Treg cell numbers and the production of IL-10 pairs were upregulated, and the production of TGF-β not was inhibited, by a mAb to SIRPα. Moreover, a mAb to SIRPα, the expression of HLA-DR and CD86 were markedly inhibited and the expression of CD80 was slightly upregulated, on the surface of CD14 + monocytes from ITP patients as compared with healthy subjects. However, blockade of SIRPα increased the secretion of TLR-dependent cytokines TNF-α, IL-6 and IL-1β by PBMCs, which may be considered as a reserve in response to danger signals. These results suggest that SIRPα on monocytes is essential for the priming of naive T cells and the development of ITP. Therefore, SIRPα is a potential therapeutic target for ITP and other autoimmune diseases.
{"title":"A mAb to SIRPα downregulates the priming of naive CD4 + T cell in Primary immune thrombocytopenia","authors":"Dongmei Xie, Zhihui Feng, Wen Yang, Yacan Wang, Renxia Li, Shiqi Zhang, Zeping Zhou","doi":"10.1016/j.cellimm.2023.104757","DOIUrl":"10.1016/j.cellimm.2023.104757","url":null,"abstract":"<div><p>SIRPα is a transmembrane protein that binds the protein tyrosine phosphatases SHP-1 and SHP-2 through its cytoplasmic region and is abundantly expressed on monocytes, dendritic cells, and macrophages. Studies recently showed that SIRPα is essential for priming of CD4 + T cells by DCs and for development of Th17 cell-mediated autoimmune diseases. We have now further evaluated the importance of SIRPα and that of its ligand CD47 in primary immune thrombocytopenia (ITP). In this study, we show that there was a low expression state of SIRPα on the surface of monocytes. Treatment of cells culture from ITP patients with a mAb to SIRPα that blocks the binding of SIRPα to CD47 downregulated the ITP response. The abilities of monocytes from ITP patients to stimulate an allogenic MLR were reduced. The proliferation of, and production of IL-2, by CD4 + T cells from ITP patients were inhibited, the Treg cell numbers and the production of IL-10 pairs were upregulated, and the production of TGF-β not was inhibited, by a mAb to SIRPα. Moreover, a mAb to SIRPα, the expression of HLA-DR and CD86 were markedly inhibited and the expression of CD80 was slightly upregulated, on the surface of CD14 + monocytes from ITP patients as compared with healthy subjects. However, blockade of SIRPα increased the secretion of TLR-dependent cytokines TNF-α, IL-6 and IL-1β by PBMCs, which may be considered as a reserve in response to danger signals. These results suggest that SIRPα on monocytes is essential for the priming of naive T cells and the development of ITP. Therefore, SIRPα is a potential therapeutic target for ITP and other autoimmune diseases.</p></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10251235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}