title: SOCS1 prevents potentially skin-reactive cytotoxic T lymphocytes from gaining the ability to cause inflammatory lesions.
abstract: Suppressor of cytokine signaling 1 (SOCS1) is a critical regulator of T lymphocyte homeostasis. SOCS1-deficient mice accumulate CD8(+) T cells, which display a memory-like phenotype and proliferate strongly to IL-15. Socs1(-/-) mice develop inflammatory skin lesions, however, the underlying mechanisms are not well understood. In order to investigate the role of SOCS1 in regulating CD8(+) T cells potentially reactive to tissue antigens (Ags) of the skin, we generated Socs1(-/-) mice expressing MHC-I-restricted Pmel-1 transgenic TCR specific to the melanoma-derived gp100 Ag, which is also expressed by normal melanocytes. Socs1(-/-) Pmel-1 cells express increased levels of memory markers CD44, Ly6C, CD122, and CD62L, and show downregulation of TCR and upregulation of CD5, suggesting in vivo TCR stimulation. However, stimulation of Socs1(-/-)Pmel-1 cells with gp100-derived peptide induced only marginal proliferation in vitro despite eliciting strong effector functions, which was associated with elevated Blimp-1 induction. Following adoptive transfer to Rag1(-/-) mice, Socs1(-/-)Pmel-1 cells underwent lymphopenia-induced proliferation and caused severe skin pathology characterized by inflammatory lesions in ears, muzzle, extremities, and eyes. These findings underscore the importance of SOCS1 in regulating potentially skin-reactive cytotoxic T lymphocytes, which could get activated under conditions that promote Ag-nonspecific, cytokine-driven proliferation.
authors: Division of Immunology, Department of Pediatrics, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Québec, Canada.
authors: Galaxia Maria
authors: GM
authors: Rodriguez
authors: Dante
authors: D
authors: D'Urbano
authors: Diwakar
authors: D
authors: Bobbala
authors: Xi Lin
authors: XL
authors: Chen
authors: Mehdi
authors: M
authors: Yeganeh
authors: Sheela
authors: S
authors: Ramanathan
authors: Subburaj
authors: S
authors: Ilangumaran
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D049109:Cell Proliferation; D003872:Dermatitis / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D018398:Homeodomain Proteins / Q000235:genetics; D018960:Hyaluronan Receptors / Q000276:immunology; D007156:Immunologic Memory / Q000276:immunology*; D053646:Interleukin-2 Receptor beta Subunit / Q000276:immunology; D019041:L-Selectin / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008231:Lymphopenia / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000074462:Positive Regulatory Domain I-Binding Factor 1; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000473:pathology; D014157:Transcription Factors / Q000276:immunology; D058951:gp100 Melanoma Antigen / Q000276:immunology
chemical_list: D000950:Antigens, Ly; C476399:Cd44 protein, mouse; D018398:Homeodomain Proteins; D018960:Hyaluronan Receptors; C508022:Il2rb protein, mouse; D053646:Interleukin-2 Receptor beta Subunit; C494192:Ly-6C antigen, mouse; C513258:Prdm1 protein, mouse; C491590:Socs1 protein, mouse; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D014157:Transcription Factors; D058951:gp100 Melanoma Antigen; D019041:L-Selectin; C064658:RAG-1 protein; D000074462:Positive Regulatory Domain I-Binding Factor 1