| First Author | Rodriguez GM | Year | 2013 |
| Journal | J Invest Dermatol | Volume | 133 |
| Issue | 8 | Pages | 2013-22 |
| PubMed ID | 23443260 | Mgi Jnum | J:198836 |
| Mgi Id | MGI:5499278 | Doi | 10.1038/jid.2013.86 |
| Citation | Rodriguez GM, et al. (2013) SOCS1 Prevents Potentially Skin-Reactive Cytotoxic T Lymphocytes from Gaining the Ability to Cause Inflammatory Lesions. J Invest Dermatol 133(8):2013-22 |
| abstractText | 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. |
