Nuclear matrix binding protein SMAR1 regulates T-cell differentiation and allergic airway disease.
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.
National Centre for Cell Science, Pune University, Pune, India.
S V
SV
Chemmannur
National Centre for Cell Science, Pune University, Pune, India.|Piramal Enterprises, Nirlon Complex, Mumbai, India.
A J
AJ
Badhwar
National Centre for Cell Science, Pune University, Pune, India.
B
B
Mirlekar
National Centre for Cell Science, Pune University, Pune, India.|University of Massachusetts Medical School, Worcester, Massachusetts, USA.
S K
SK
Malonia
National Centre for Cell Science, Pune University, Pune, India.
M
M
Gupta
National Institute of Immunology, New Delhi, India.
N
N
Wadhwa
National Centre for Cell Science, Pune University, Pune, India.
R
R
Bopanna
CSIR-Institute of Genomic and Integrative Biology, New Delhi, India.
U
U
Mabalirajan
National Institute of Immunology, New Delhi, India.
S
S
Majumdar
CSIR-Institute of Genomic and Integrative Biology, New Delhi, India.
B
B
Ghosh
National Centre for Cell Science, Pune University, Pune, India.
S
S
Chattopadhyay
D000818:Animals; D001249:Asthma / Q000276:immunology*; D015153:Blotting, Western; D018797:Cell Cycle Proteins / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology*; D047369:Chromatin Immunoprecipitation; D004268:DNA-Binding Proteins / Q000276:immunology*; D004195:Disease Models, Animal; D024202:Electrophoretic Mobility Shift Assay; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006967:Hypersensitivity / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009687:Nuclear Proteins / Q000276:immunology*; D060888:Real-Time Polymerase Chain Reaction; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000276:immunology*
C485952:Banp protein, mouse; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins