title: SOCS3 promotes interleukin-17 expression of human T cells.
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.
authors.affiliation: Department of Immunology, Bernhard-Nocht-Institute for Tropical Medicine, Hamburg, Germany.
authors.forename: Katja
authors.initials: K
authors.lastname: Kleinsteuber
authors.forename: Kerrin
authors.initials: K
authors.lastname: Heesch
authors.forename: Stefanie
authors.initials: S
authors.lastname: Schattling
authors.forename: Claudia
authors.initials: C
authors.lastname: Sander-Juelch
authors.forename: Ulrike
authors.initials: U
authors.lastname: Mock
authors.forename: Kristoffer
authors.initials: K
authors.lastname: Riecken
authors.forename: Boris
authors.initials: B
authors.lastname: Fehse
authors.forename: Bernhard
authors.initials: B
authors.lastname: Fleischer
authors.forename: Marc
authors.initials: M
authors.lastname: Jacobsen
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D006801:Humans; D020381:Interleukin-17 / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000235:genetics; D009169:Mycobacterium tuberculosis / Q000276:immunology; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D037182:T-Cell Antigen Receptor Specificity / Q000187:drug effects / Q000235:genetics; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000502:physiology; D014162:Transfection; D014376:Tuberculosis / Q000276:immunology; D015854:Up-Regulation / Q000235:genetics
chemical_list: D020381:Interleukin-17; C106644:SOCS3 protein, human; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins