Year : 2015 | Volume
: 142 | Issue : 4 | Page : 405--413
Regulation of T cell lineage commitment by SMAR1 during inflammatory & autoimmune diseases
Bhalchandra Mirlekar1, Subeer Majumdar2, Madhukar Khetmalas3, Samit Chattopadhyay1
1 Chromatin & Disease Biology Laboratory, National Centre for Cell Science, Pune, India
2 National Institute of Immunology, New Delhi, India
3 D.Y. Patil Institute of Bioinformatics & Biotechnology, Pune, India
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.
Chromatin & Disease Biology Laboratory, National Centre for Cell Science, Ganeshkhind, Pune 411 007, Maharashtra
|How to cite this article:|
Mirlekar B, Majumdar S, Khetmalas M, Chattopadhyay S. Regulation of T cell lineage commitment by SMAR1 during inflammatory & autoimmune diseases.Indian J Med Res 2015;142:405-413
|How to cite this URL:|
Mirlekar B, Majumdar S, Khetmalas M, Chattopadhyay S. Regulation of T cell lineage commitment by SMAR1 during inflammatory & autoimmune diseases. Indian J Med Res [serial online] 2015 [cited 2020 Nov 24 ];142:405-413
Available from: https://www.ijmr.org.in/article.asp?issn=0971-5916;year=2015;volume=142;issue=4;spage=405;epage=413;aulast=Mirlekar;type=0