Regulation of T cell lineage commitment by SMAR1 during inflammatory & autoimmune diseases

Mirlekar, Bhalchandra ; Majumdar, Subeer ; Khetmalas, Madhukar ; Chattopadhyay, Samit (2015) Regulation of T cell lineage commitment by SMAR1 during inflammatory & autoimmune diseases Indian Journal of Medical Research, 142 (4). pp. 405-413. ISSN 0971-5916

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Official URL: http://ijmr.org.in/article.asp?issn=0971-5916;year...

Related URL: http://dx.doi.org/10.4103/0971-5916.169198

Abstract

Background & objectives: 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. Interpretation & 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.

Item Type:Article
Source:Copyright of this article belongs to Indian Council of Medical Research.
Keywords:Colitis; IL-17; Rheumatoid Arthritis; RORγt; SMAR1; T Cell Differentiation
ID Code:104552
Deposited On:20 Feb 2017 07:24
Last Modified:02 Feb 2018 03:38

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