TY - JOUR
T1 - Treg-specific deletion of NKAP results in severe, systemic autoimmunity due to peripheral loss of Tregs
AU - Dash, Barsha
AU - Shapiro, Michael J.
AU - Chung, Ji Young
AU - Romero Arocha, Sinibaldo
AU - Shapiro, Virginia Smith
N1 - Publisher Copyright:
© 2018 Elsevier Ltd
PY - 2018/5
Y1 - 2018/5
N2 - 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.
AB - 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.
KW - Complement
KW - NKAP
KW - Scurfy
KW - Tregs
UR - http://www.scopus.com/inward/record.url?scp=85040639823&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85040639823&partnerID=8YFLogxK
U2 - 10.1016/j.jaut.2017.12.013
DO - 10.1016/j.jaut.2017.12.013
M3 - Article
C2 - 29366602
AN - SCOPUS:85040639823
SN - 0896-8411
VL - 89
SP - 139
EP - 148
JO - Journal of Autoimmunity
JF - Journal of Autoimmunity
ER -