2015
Mucosal Immunol. 2015 Mar 4. doi: 10.1038/mi.2015.11. [Epub ahead of print]
Nuclear matrix binding protein SMAR1 regulates T-cell differentiation and allergic airway disease.
National Centre for Cell Science, Pune University, Pune, India. Piramal Enterprises, Nirlon Complex, Mumbai, India. University of Massachusetts Medical School, Worcester, Massachusetts, USA. National Institute of Immunology, New Delhi, India. 5CSIR-Institute of Genomic and Integrative Biology, New Delhi, India.
Service type: Knockout mice
Abstract
Asthma is a complex airway allergic disease involving the interplay of various cell types, cytokines, and transcriptional factors. Though many factors contribute to disease etiology, the molecular control of disease phenotype and responsiveness is not well understood. Here we report an essential role of the matrix attachment region (MAR)-binding protein SMAR1 in regulating immune response during allergic airway disease. Conditional knockout of SMAR1 in T cells rendered the mice resistant to eosinophilic airway inflammation against ovalbumin (OVA) allergen with low immunoglobulin E (IgE) and interleukin-5 (IL-5) levels. Moreover, a lower IgE/IgG2a ratio and higher interferon-γ (IFN-γ) response suggested aberrant skewing of T-cell differentiation toward type 1 helper T cell (Th1) response. We show that SMAR1 functions as a negative regulator of Th1 and Th17 differentiation by interacting with two potential and similar MAR regions present on the promoters of T-bet and IL-17. Thus, we present SMAR1 as a regulator of T-cell differentiation that favors the establishment of Th2 cells by modulating Th1 and Th17 responses.
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