蛋白酪氨酸磷酸酶非受体型22（PTPN22）在慢性病毒感染期间导致T淋巴细胞耗竭。
PTPN22 contributes to exhaustion of T lymphocytes during chronic viral infection.
作者信息
Maine Christian J, Teijaro John R, Marquardt Kristi, Sherman Linda A
机构信息
Department of Immunology and Microbial Sciences, The Scripps Research Institute, La Jolla, CA 92037.
Department of Immunology and Microbial Sciences, The Scripps Research Institute, La Jolla, CA 92037
出版信息
Proc Natl Acad Sci U S A. 2016 Nov 15;113(46):E7231-E7239. doi: 10.1073/pnas.1603738113. Epub 2016 Oct 31.
The protein encoded by the autoimmune-associated protein tyrosine phosphatase nonreceptor type 22 gene, PTPN22, has wide-ranging effects in immune cells including suppression of T-cell receptor signaling and promoting efficient production of type I interferons (IFN-I) by myeloid cells. Here we show that mice deficient in PTPN22 resist chronic viral infection with lymphocytic choriomeningitis virus clone 13 (LCMV cl13). The numbers and function of viral-specific CD4 T lymphocytes is greatly enhanced, whereas expression of the IFNβ-induced IL-2 repressor, cAMP-responsive element modulator (CREM) is reduced. Reduction of CREM expression in wild-type CD4 T lymphocytes prevents the loss of IL-2 production by CD4 T lymphocytes during infection with LCMV cl13. These findings implicate the IFNβ/CREM/IL-2 axis in regulating T-lymphocyte function during chronic viral infection.
自身免疫相关蛋白酪氨酸磷酸酶非受体22型基因（PTPN22）编码的蛋白质在免疫细胞中具有广泛作用，包括抑制T细胞受体信号传导以及促进髓样细胞高效产生I型干扰素（IFN-I）。在此我们表明，缺乏PTPN22的小鼠对淋巴细胞性脉络丛脑膜炎病毒克隆13（LCMV cl13）的慢性病毒感染具有抵抗力。病毒特异性CD4 T淋巴细胞的数量和功能大大增强，而IFNβ诱导的IL-2阻遏物、cAMP反应元件调节剂（CREM）的表达则降低。野生型CD4 T淋巴细胞中CREM表达的降低可防止LCMV cl13感染期间CD4 T淋巴细胞IL-2产生的丧失。这些发现表明IFNβ/CREM/IL-2轴在慢性病毒感染期间调节T淋巴细胞功能。
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