Nuclear matrix binding protein SMAR1 regulates T-cell differentiation and allergic airway disease

• Published in: Mucosal immunology Vol. 8; no. 6; pp. 1201 - 1211
• Main Authors: Chemmannur, S V, Badhwar, A J, Mirlekar, B, Malonia, S K, Gupta, M, Wadhwa, N, Bopanna, R, Mabalirajan, U, Majumdar, S, Ghosh, B, Chattopadhyay, S
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.11.2015; Elsevier Limited; Nature Publishing Group
• Subjects: 631/250/249/2510/31; 631/250/347; 692/699/249/2510/9; Allergology; Animals; Antibodies; Asthma - immunology; Biomedical and Life Sciences; Biomedicine; Blotting, Western; Cell Cycle Proteins - immunology; Cell Differentiation - immunology; Chromatin Immunoprecipitation; Disease Models, Animal; DNA-Binding Proteins - immunology; Electrophoretic Mobility Shift Assay; Flow Cytometry; Fluorescent Antibody Technique; Gastroenterology; Hypersensitivity - immunology; Immunology; Mice; Mice, Inbred C57BL; Mice, Knockout; Nuclear Proteins - immunology; Real-Time Polymerase Chain Reaction; T-Lymphocytes, Helper-Inducer - cytology; T-Lymphocytes, Helper-Inducer - immunology
• ISSN: 1933-0219; 1935-3456
• DOI: 10.1038/mi.2015.11

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.