Treg-specific deletion of NKAP results in severe, systemic autoimmunity due to peripheral loss of Tregs.
Treg-specific deletion of NKAP results in severe, systemic autoimmunity due to peripheral loss of Tregs.
J Autoimmun. 2018 Jan 20;:
Authors: Dash B, Shapiro MJ, Chung JY, Romero Arocha S, Shapiro VS
Abstract
Regulatory T cells are critical for the generation and maintenance of peripheral tolerance. Conditional deletion of the transcriptional repressor NKAP in Tregs using Foxp3-YFP-cre NKAP conditional knockout mice causes aggressive autoimmunity characterized by thymic atrophy, lymphadenopathy, peripheral T cell activation, generation of autoantibodies, immune infiltration into several organs, and crusty skin at 3 weeks of age, similar to that of "scurfy" Foxp3-mutant mice. While Treg development in the thymus proceeds normally in the absence of NKAP, there is a severe loss of thymically-derived Tregs in the periphery. NKAP-deficient Tregs have a recent thymic emigrant phenotype, and are attacked by complement in a cell-intrinsic manner in the periphery. Previously, we demonstrated that NKAP is required for conventional T cell maturation as it prevents complement-mediated attack in the periphery. We now show that Tregs undergo a similar maturation process as conventional T cells, requiring NKAP to acquire complement resistance after thymic egress.
PMID: 29366602 [PubMed - as supplied by publisher]
Source: Journal of Autoimmunity - Category: Allergy & Immunology Authors: Dash B, Shapiro MJ, Chung JY, Romero Arocha S, Shapiro VS Tags: J Autoimmun Source Type: research
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