SOCS3 promotes interleukin-17 expression of human T cells.
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SOCS3 promotes interleukin-17 expression of human T cells. / Kleinsteuber, Katja; Heesch, Kerrin; Schattling, Stefanie; Sander-Juelch, Claudia; Mock, Ulrike; Riecken, Kristoffer; Fehse, Boris; Fleischer, Bernhard; Jacobsen, Marc.
In: BLOOD, Vol. 120, No. 22, 22, 2012, p. 4374-4382.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - SOCS3 promotes interleukin-17 expression of human T cells.
AU - Kleinsteuber, Katja
AU - Heesch, Kerrin
AU - Schattling, Stefanie
AU - Sander-Juelch, Claudia
AU - Mock, Ulrike
AU - Riecken, Kristoffer
AU - Fehse, Boris
AU - Fleischer, Bernhard
AU - Jacobsen, Marc
PY - 2012
Y1 - 2012
N2 - 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.
AB - 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.
KW - Humans
KW - Gene Expression Regulation
KW - Cells, Cultured
KW - Flow Cytometry
KW - Transfection
KW - Cell Proliferation/drug effects
KW - Up-Regulation/genetics
KW - CD4-Positive T-Lymphocytes/drug effects/metabolism/physiology
KW - Interleukin-17/genetics/metabolism/pharmacology
KW - Lymphocyte Activation/genetics
KW - Mycobacterium tuberculosis/immunology
KW - Suppressor of Cytokine Signaling Proteins/genetics/metabolism/physiology
KW - T-Cell Antigen Receptor Specificity/drug effects/genetics
KW - T-Lymphocytes/drug effects/immunology/metabolism/physiology
KW - Tuberculosis/immunology
KW - Humans
KW - Gene Expression Regulation
KW - Cells, Cultured
KW - Flow Cytometry
KW - Transfection
KW - Cell Proliferation/drug effects
KW - Up-Regulation/genetics
KW - CD4-Positive T-Lymphocytes/drug effects/metabolism/physiology
KW - Interleukin-17/genetics/metabolism/pharmacology
KW - Lymphocyte Activation/genetics
KW - Mycobacterium tuberculosis/immunology
KW - Suppressor of Cytokine Signaling Proteins/genetics/metabolism/physiology
KW - T-Cell Antigen Receptor Specificity/drug effects/genetics
KW - T-Lymphocytes/drug effects/immunology/metabolism/physiology
KW - Tuberculosis/immunology
M3 - SCORING: Journal article
VL - 120
SP - 4374
EP - 4382
JO - BLOOD
JF - BLOOD
SN - 0006-4971
IS - 22
M1 - 22
ER -
