title: Suppressor of cytokine signaling (SOCS) proteins are induced by IL-7 and target surface CD127 protein for degradation in human CD8 T cells.
abstract: Given the essential role interleukin (IL)-7 plays in T-cell survival, homeostasis and function, it is no surprise expression of the IL-7 receptor alpha-chain (CD127) is tightly regulated. We have previously shown IL-7 binding to its receptor on the surface of CD8 T cells leads to both suppression of CD127 gene transcription and loss of existing CD127 protein from the cell membrane. Indeed upon binding IL-7, CD127 is rapidly internalized into early endosomes where phosphorylation by JAK targets the receptor for degradation. We now show that IL-7 induces the expression of suppressor of cytokine signaling (SOCS) proteins CIS, SOCS1 and SOCS2 through the JAK/STAT-5 pathway and that CIS and SOCS2 specifically interact with CD127 in early endosomes and direct the receptor complex to the proteasome for degradation. These results illustrate how expression of the IL-7 receptor and thus IL-7 signaling is modulated in human CD8 T cells by a negative feedback mechanism dependent on members of the SOCS family of proteins.
authors.affiliation: Ottawa Hospital Research Institute, 501 Smyth Road, Ottawa, Ontario K1H 8L6, Canada; Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, 451 Smyth Road, Ottawa, Ontario K1H 8M5, Canada.
authors.forename: Feras M
authors.initials: FM
authors.lastname: Ghazawi
authors.affiliation: Ottawa Hospital Research Institute, 501 Smyth Road, Ottawa, Ontario K1H 8L6, Canada; Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, 451 Smyth Road, Ottawa, Ontario K1H 8M5, Canada.
authors.forename: Elliott M
authors.initials: EM
authors.lastname: Faller
authors.affiliation: Ottawa Hospital Research Institute, 501 Smyth Road, Ottawa, Ontario K1H 8L6, Canada; Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, 451 Smyth Road, Ottawa, Ontario K1H 8M5, Canada.
authors.forename: Parmvir
authors.initials: P
authors.lastname: Parmar
authors.affiliation: Ottawa Hospital Research Institute, 501 Smyth Road, Ottawa, Ontario K1H 8L6, Canada; Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, 451 Smyth Road, Ottawa, Ontario K1H 8M5, Canada.
authors.forename: Abdulkareem
authors.initials: A
authors.lastname: El-Salfiti
authors.affiliation: Ottawa Hospital Research Institute, 501 Smyth Road, Ottawa, Ontario K1H 8L6, Canada; Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, 451 Smyth Road, Ottawa, Ontario K1H 8M5, Canada; Division of Infectious Diseases, Ottawa Hospital General Campus, 501 Smyth Road, Ottawa, Ontario K1H 8L6, Canada. Electronic address: pmacpherson@toh.ca.
authors.forename: Paul A
authors.initials: PA
authors.lastname: MacPherson
mesh_terms: D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D011992:Endosomes / Q000378:metabolism; D006801:Humans; D015851:Interleukin-7 / Q000378:metabolism*; D053699:Interleukin-7 Receptor alpha Subunit / Q000378:metabolism*; D053612:Janus Kinases / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011485:Protein Binding; D059748:Proteolysis; D050799:STAT5 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D000071222:Suppressor of Cytokine Signaling 1 Protein / Q000235:genetics / Q000378:metabolism*; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D015851:Interleukin-7; D053699:Interleukin-7 Receptor alpha Subunit; D053612:Janus Kinases; D046988:Proteasome Endopeptidase Complex; D050799:STAT5 Transcription Factor; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; C508605:IL7 protein, human; C108944:SOCS1 protein, human; C106643:SOCS2 protein, human
keywords: CD127; CD8 T cells; CIS; IL-7 receptor; Interleukin-7; SOCS; SOCS2