The transcription factor Foxp1 is a critical negative regulator of the differentiation of follicular helper T cells.

Autor: Wang H; The Wistar Institute, Philadelphia, Pennsylvania, USA., Geng J; 1] The Wistar Institute, Philadelphia, Pennsylvania, USA. [2]., Wen X; 1] The Wistar Institute, Philadelphia, Pennsylvania, USA. [2]., Bi E; The Wistar Institute, Philadelphia, Pennsylvania, USA., Kossenkov AV; The Wistar Institute, Philadelphia, Pennsylvania, USA., Wolf AI; The Wistar Institute, Philadelphia, Pennsylvania, USA., Tas J; Whitehead Institute for Biomedical Research, Cambridge, Massachusetts, USA., Choi YS; La Jolla Institute for Allergy & Immunology, La Jolla, California, USA., Takata H; The Wistar Institute, Philadelphia, Pennsylvania, USA., Day TJ; The Wistar Institute, Philadelphia, Pennsylvania, USA., Chang LY; The Wistar Institute, Philadelphia, Pennsylvania, USA., Sprout SL; The Wistar Institute, Philadelphia, Pennsylvania, USA., Becker EK; The Wistar Institute, Philadelphia, Pennsylvania, USA., Willen J; The Wistar Institute, Philadelphia, Pennsylvania, USA., Tian L; The Wistar Institute, Philadelphia, Pennsylvania, USA., Wang X; The Wistar Institute, Philadelphia, Pennsylvania, USA., Xiao C; Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, California, USA., Jiang P; The Wistar Institute, Philadelphia, Pennsylvania, USA., Crotty S; La Jolla Institute for Allergy & Immunology, La Jolla, California, USA., Victora GD; Whitehead Institute for Biomedical Research, Cambridge, Massachusetts, USA., Showe LC; The Wistar Institute, Philadelphia, Pennsylvania, USA., Tucker HO; Department of Molecular Genetics and The Institute for Cellular and Molecular Biology, The University of Texas at Austin, Texas, USA., Erikson J; The Wistar Institute, Philadelphia, Pennsylvania, USA., Hu H; The Wistar Institute, Philadelphia, Pennsylvania, USA.
Jazyk: angličtina
Zdroj: Nature immunology [Nat Immunol] 2014 Jul; Vol. 15 (7), pp. 667-75. Date of Electronic Publication: 2014 May 25.
DOI: 10.1038/ni.2890
Abstrakt: CD4(+) follicular helper T cells (T(FH) cells) are essential for germinal center (GC) responses and long-lived antibody responses. Here we report that naive CD4(+) T cells deficient in the transcription factor Foxp1 'preferentially' differentiated into T(FH) cells, which resulted in substantially enhanced GC and antibody responses. We found that Foxp1 used both constitutive Foxp1A and Foxp1D induced by stimulation of the T cell antigen receptor (TCR) to inhibit the generation of T(FH) cells. Mechanistically, Foxp1 directly and negatively regulated interleukin 21 (IL-21); Foxp1 also dampened expression of the costimulatory molecule ICOS and its downstream signaling at early stages of T cell activation, which rendered Foxp1-deficient CD4(+) T cells partially resistant to blockade of the ICOS ligand (ICOSL) during T(FH) cell development. Our findings demonstrate that Foxp1 is a critical negative regulator of T(FH) cell differentiation.
Databáze: MEDLINE