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 Smith Shapiro

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


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)
Pages (from-to)139-148
Number of pages10
JournalJournal of Autoimmunity
StatePublished - May 2018


  • Complement
  • NKAP
  • Scurfy
  • Tregs

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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