title: Regulation of T cell lineage commitment by SMAR1 during inflammatory & autoimmune diseases.
abstract: OBJECTIVE
  CD4 + T cells are involved in abnormal inflammatory responses causing adverse effects to the body. Th17 cells play a major role in immune disorders and the exact mechanism by which CD4 + T cells regulate its effector Th1 and Th17 phenotype at chromatin level is not clearly understood. This study was aimed to understand the role of matrix associated region (MAR) binding protein SMAR1 (scaffold/matrix attachment region binding protein 1) in T cell differentiation during inflammatory and autoimmune condition using SMAR1 transgenic mice as model.
  
  
  METHODS
  Wild type (C57BL/6J) and SMAR1 transgenic mice were used for isolation of T cells and further identification of different T cell lineages, along with histological analysis. Further, we studied autoimmune and inflammatory diseases using chemically induced and T cell transfer model of colitis and rheumatoid arthritis to better understand the role of SMAR1 in immune responses.
  
  
  RESULTS
  SMAR1 transgenic mice were resistant to dextran sodium sulphate (DSS) induced colitis with decreased expression of Th1 and Th17 specific cytokines. Overexpression of SMAR1 repressed Th17 response by negatively regulating RORγt and IL-17 expression. Downregulation of SMAR1 upregulated signal transducer and activator of transcription 3 (pSTAT3) and IL-17 expression that caused generation of more proinflammatory Th1 and Th17 cells leading to inflammation and disease.
  
  
  CONCLUSIONS
  Our results show an important role of SMAR1 in regulating CD4 + T cell differentiation during inflammatory disorders via regulation of both Th1 and Th17 signaling pathways. This study reveals a critical role of SMAR1 in maintaining the proinflammatory immune responses by repressing Th1 and Th17 cell function and it gives the novel insight into immune regulatory mechanisms.
authors.forename: Bhalchandra
authors.initials: B
authors.lastname: Mirlekar
authors.forename: Subeer
authors.initials: S
authors.lastname: Majumdar
authors.forename: Madhukar
authors.initials: M
authors.lastname: Khetmalas
authors.affiliation: Chromatin & Disease Biology Laboratory, National Centre for Cell Science, Pune, India.
authors.forename: Samit
authors.initials: S
authors.lastname: Chattopadhyay
mesh_terms: D000818:Animals; D001172:Arthritis, Rheumatoid / Q000139:chemically induced / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D018797:Cell Cycle Proteins / Q000096:biosynthesis* / Q000235:genetics; D019070:Cell Lineage / Q000235:genetics / Q000276:immunology; D002843:Chromatin / Q000235:genetics / Q000276:immunology; D003092:Colitis / Q000139:chemically induced / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D016264:Dextran Sulfate / Q000633:toxicity; D004195:Disease Models, Animal; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D020381:Interleukin-17 / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D009687:Nuclear Proteins / Q000096:biosynthesis* / Q000235:genetics; D050796:STAT3 Transcription Factor / Q000096:biosynthesis / Q000235:genetics; D018417:Th1 Cells / Q000276:immunology / Q000473:pathology; D058504:Th17 Cells / Q000276:immunology* / Q000473:pathology
chemical_list: C485952:Banp protein, mouse; D018797:Cell Cycle Proteins; D002843:Chromatin; D004268:DNA-Binding Proteins; D020381:Interleukin-17; D009687:Nuclear Proteins; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D016264:Dextran Sulfate