AUTHOR=Zhou Yan , Leng Xiao , He Yan , Li Yan , Liu Yuan , Liu Yang , Zou Qiang , Shi Guixiu , Wang Yantang 

TITLE=Loss of Perp in T Cells Promotes Resistance to Apoptosis of T Helper 17 Cells and Exacerbates the Development of Experimental Autoimmune Encephalomyelitis in Mice

JOURNAL=Frontiers in Immunology

VOLUME=9

YEAR=2018

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2018.00842

DOI=10.3389/fimmu.2018.00842

ISSN=1664-3224

ABSTRACT=<p>T helper 17 (Th17) cells are crucial for the pathogenesis of multiple sclerosis (MS) in humans and experimental autoimmune encephalomyelitis (EAE) in animals. High frequency of Th17 cells and low sensitivity to activation-induced cell death (AICD) are detected in MS patients. However, the mechanisms underlying apoptosis resistance of T cells remain unclear. <italic>Perp</italic> is an apoptosis-associated target of <italic>p53</italic> and implicated in the development of cancers. Here, we show that loss of <italic>Perp</italic> in T cells does not affect Th1, Th17, or Treg cell differentiation, but does significantly increase the resistance of <italic>Perp</italic><sup>−/−</sup> Th17 cells to AICD and anti-Fas in Lck-Cre × <italic>Perp</italic><sup>fl/fl</sup> mice by inhibiting the caspase-dependent apoptotic pathway. Moreover, Lck-Cre × <italic>Perp</italic><sup>fl/fl</sup> mice exhibited earlier onset of EAE and severe spinal cord inflammation and demyelination, accompanied by increased levels of pro-inflammatory cytokines and enlarged population of Th17 cells. Therefore, <italic>Perp</italic> deletion promoted Th17 responses and exacerbated the development and severity of EAE.</p>