| First Author | Collins EL | Year | 2011 |
| Journal | J Immunol | Volume | 187 |
| Issue | 5 | Pages | 2666-76 |
| PubMed ID | 21788442 | Mgi Jnum | J:179143 |
| Mgi Id | MGI:5301200 | Doi | 10.4049/jimmunol.1003819 |
| Citation | Collins EL, et al. (2011) Inhibition of SOCS1-/- lethal autoinflammatory disease correlated to enhanced peripheral Foxp3+ regulatory T cell homeostasis. J Immunol 187(5):2666-76 |
| abstractText | Suppressor of cytokine signaling 1-deficient (SOCS1(-/-)) mice, which are lymphopenic, die <3 wk after birth of a T cell-mediated autoimmune inflammatory disease characterized by leukocyte infiltration and destruction of vital organs. Notably, Foxp3(+) regulatory T cells (Tregs) have been shown to be particularly potent in inhibiting inflammation-associated autoimmune diseases. We observed that SOCS1(-/-) mice were deficient in peripheral Tregs despite enhanced thymic development. The adoptive transfer of SOCS1-sufficient Tregs, CD4(+) T lymphocytes, or administration of SOCS1 kinase inhibitory region (KIR), a peptide that partially restores SOCS1 function, mediated a statistically significant but short-term survival of SOCS1(-/-) mice. However, the adoptive transfer of SOCS1-sufficient CD4(+) T lymphocytes, combined with the administration of SOCS1-KIR, resulted in a significant increase in the survival of SOCS1(-/-) mice both short and long term, where 100% death occurred by day 18 in the absence of treatment. Moreover, the CD4(+)/SOCS1-KIR combined therapy resulted in decreased leukocytic organ infiltration, reduction of serum IFN-gamma, and enhanced peripheral accumulation of Foxp3(+) Tregs in treated mice. These data show that CD4(+)/SOCS1-KIR combined treatment can synergistically promote the long-term survival of perinatal lethal SOCS1(-/-) mice. In addition, these results strongly suggest that SOCS1 contributes to the stability of the Foxp3(+) Treg peripheral population under conditions of strong proinflammatory environments. |
