Treg-specific deletion of NKAP results in severe, systemic autoimmunity due to peripheral loss of Tregs

Barsha Dash, Michael J. Shapiro, Ji Young Chung, Sinibaldo Romero Arocha, Virginia M Shapiro

Research output: Contribution to journalArticle

6 Citations (Scopus)

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.

Original languageEnglish (US)
JournalJournal of Autoimmunity
DOIs
StateAccepted/In press - Jan 1 2018

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Autoimmunity
T-Lymphocytes
Peripheral Tolerance
Regulatory T-Lymphocytes
Knockout Mice
Autoantibodies
Thymus Gland
Atrophy
Maintenance
Phenotype
Skin

Keywords

  • Complement
  • NKAP
  • Scurfy
  • Tregs

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Treg-specific deletion of NKAP results in severe, systemic autoimmunity due to peripheral loss of Tregs. / Dash, Barsha; Shapiro, Michael J.; Chung, Ji Young; Romero Arocha, Sinibaldo; Shapiro, Virginia M.

In: Journal of Autoimmunity, 01.01.2018.

Research output: Contribution to journalArticle

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