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THE JOURNAL OF BIOLOGICAL CHEMISTRY VOL. 288, NO. 38, pp. 274237433, September 20, 2013 2013 by The American Society for Biochemistry and Molecular Biology, Inc. Published in the U.S.A.The Somatostatin Receptor Synonyms transcription Aspect Twist1 Limits T Helper 17 and T Follicular Helper Cell Improvement by Repressing the Gene Encoding the Interleukin-6 Receptor ChainReceived for publication, June 26, 2013, and in revised type, August 9, 2013 Published, JBC Papers in Press, August 9, 2013, DOI 10.1074/jbc.M113.Duy Pham, Crystal C. Walline, Kristin Hollister1, Alexander L. Dent, Janice S. Blum Anthony B. Firulli, and Mark H. Kaplan In the Division of Pediatrics, Herman B. Wells Center for Pediatric Investigation and �Department of Microbiology and Immunology, Indiana University College of Medicine, Indianapolis, IndianaBackground: Twist1 is often a transcriptional repressor that inhibits the improvement of Th1 cells. Final results: Twist1 impairs Th17 and Tfh cell development by decreasing IL-6-induced STAT3. NMDA Receptor list Conclusion: Twist1 represses the improvement of autoimmunity and germinal center B cell expansion and antibody production following immunization. Significance: Twist1 can be a prevalent repressor of cell-mediated and humoral adaptive immunity. Cytokine responsiveness is usually a important element from the potential of cells to respond towards the extracellular milieu. Transcription factor-mediated regulation of cytokine receptor expression is a common mode of altering responses for the external environment. We identify the transcription issue Twist1 as a component of a STAT3-induced feedback loop that controls IL-6 signals by directly repressing Il6ra. Human and mouse T cells lacking Twist1 have an enhanced capability to differentiate into Th17 cells. Mice using a T cell-specific deletion of Twist1 demonstrate elevated Th17 and T follicular helper cell improvement, early onset experimental autoimmune encephalomyelitis, and elevated antigen-specific antibody responses. Hence, Twist1 includes a vital part in limiting each cell-mediated and humoral immunity.CD4 T helper cells handle immunity to pathogens and also the improvement of inflammatory illness by acquiring the capability to secrete effector cytokines. The differentiation of T helper subsets follows exposure to a specific cytokine environment. IL-12 promotes improvement of Th1 cells, IL-4 promotes Th2 differentiation, and there are actually partially redundant roles for IL-6 and IL-21 in T follicular helper (Tfh)3 cell improvement (1, 2). Th17 cells create in response to various cytokines, including IL-6, Thiswork was supported by National Institutes of Well being Grants R01AI045515 (to M. H. K.), R01 AR061392 (to A. B. F.), R21 AI099825 (to A. L. D.), P01 AI056097 (to M. H. K. and J. S. B.), R01 AI079065 (to J. S. B.), and P30 DK090948. 1 Supported by National Institutes of Well being Grant T32 HL007910. two To whom correspondence need to be addressed: Depts. of Pediatrics and Microbiology and Immunology, Indiana University College of Medicine, Herman B. Wells Center for Pediatric Study, 1044 West Walnut St., Rm. 202, Indianapolis, IN 46202. Tel.: 317-278-3696; E-mail: mkaplan2@ iupui.edu. three The abbreviations made use of are: Tfh, T follicular helper; SRBC, sheep red blood cell(s); MOG, myelin oligodendrocyte glycoprotein; EAE, experimental autoimmune encephalomyelitis; nTreg, all-natural regulatory T cells; qRTPCR, quantitative real-time PCR; Treg, regulatory.
