SOCS3 promotes interleukin-17 expression of human T cells
- 22 November 2012
- journal article
- Published by American Society of Hematology in Blood
- Vol. 120 (22), 4374-4382
- https://doi.org/10.1182/blood-2011-11-392738
Abstract
SOCS3 is a feedback regulator of cytokine signaling that affects T-cell polarization. Human tuberculosis is accompanied by increased SOCS3 expression in T cells, and this may influence susceptibility against Mycobacterium tuberculosis. Because the role of SOCS3 in human T-cell function is not well defined, we characterized cytokine expression and proliferation of human T cells with differential SOCS3 expression in the present study. We established a flow cytometry–based method for SOCS3 protein quantification and detected higher SOCS3 levels induced by M tuberculosis specific T-cell activation and a transient decrease of SOCS3 expression in the presence of mycobacteria-infected macrophages. Notably increased SOCS3 expression was detected in IL-17–expressing T-cell clones and in CD161+ T helper type 17 cells ex vivo. Ectopic SOCS3 expression in primary CD4+ T cells by lentiviral transduction induced increased IL-17 production but diminished proliferation and viability. Recombinant IL-7 inhibited SOCS3 expression and reduced IL-17–expressing T-cell proportions. We concluded that higher SOCS3 expression in human T cells favors T helper type 17 cells. Therefore, increased SOCS3 expression in human tuberculosis may reflect polarization toward IL-17–expressing T cells as well as T-cell exhaustion marked by reduced proliferation.This publication has 44 references indexed in Scilit:
- The many faces of Th17 cellsCurrent Opinion in Immunology, 2011
- Suppressor of cytokine signaling-3 is affected in T-cells from tuberculosisTB patientsClinical Microbiology & Infection, 2011
- Epigenetic Instability of Cytokine and Transcription Factor Gene Loci Underlies Plasticity of the T Helper 17 Cell LineageImmunity, 2010
- Suppressors of cytokine signaling (SOCS) in T cell differentiation, maturation, and functionTrends in Immunology, 2009
- Loss of SOCS3 expression in T cells reveals a regulatory role for interleukin-17 in atherosclerosisThe Journal of Experimental Medicine, 2009
- TGF-β Promotes Th17 Cell Development through Inhibition of SOCS3The Journal of Immunology, 2009
- Late Developmental Plasticity in the T Helper 17 LineageImmunity, 2009
- Human interleukin 17-producing cells originate from a CD161(+)CD4(+) T cell precursorThe Journal of Experimental Medicine, 2008
- Selective regulatory function of Socs3 in the formation of IL-17-secreting T cellsProceedings of the National Academy of Sciences of the United States of America, 2006
- Loss of SOCS3 in T helper cells resulted in reduced immune responses and hyperproduction of interleukin 10 and transforming growth factor–β1The Journal of Experimental Medicine, 2006