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Protein tyrosine phosphatase PTPN22 has dual roles in promoting pathogen versus homeostatic‐driven CD8 T‐cell responses
Author(s) -
Jofra Tatiana,
Di Fonte Roberta,
Hutchinson Tarun Edgar,
Dastmalchi Farhad,
Galvani Giuseppe,
Battaglia Manuela,
SalekArdakani Shahram,
Fousteri Georgia
Publication year - 2017
Publication title -
immunology and cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.999
H-Index - 104
eISSN - 1440-1711
pISSN - 0818-9641
DOI - 10.1038/icb.2016.92
Subject(s) - protein tyrosine phosphatase , biology , lymphocytic choriomeningitis , microbiology and biotechnology , t cell , cytotoxic t cell , zap70 , interferon , cd8 , immune system , il 2 receptor , signal transduction , immunology , in vitro , biochemistry
PTPN22 (protein tyrosine phosphatase non receptor 22) encodes a tyrosine phosphatase that functions as a key regulator of immune homeostasis. In particular, PTPN22 inhibits T‐cell receptor signaling and selectively promotes type I interferon responses in myeloid cells. To date, there is little information on the CD8 T‐cell‐intrinsic role of PTPN22 in response to a viral pathogen. We unexpectedly found that PTPN22‐deficient virus‐specific CD8 T cells failed to accumulate in wild‐type hosts after lymphocytic choriomeningitis virus infection. Lack of PTPN22 expression altered CD8 T‐cell activation and antiviral cytokine production, but did not significantly affect the composition of effector and memory cell precursors. Most significantly, in vivo , PTPN22‐deficient CD8 T cells showed a profound defect in upregulating STAT‐1 after lymphocytic choriomeningitis virus infection and considerably less phosphorylation of STAT‐1 in response to IFN‐α treatment in vitro compared with their wild‐type counterparts. In stark contrast, following transfer into lymphopenic mice, CD8 T‐cell expansion and central‐like phenotype, was considerably increased in the absence of PTPN22. Collectively, our results suggest that PTPN22 has dual roles in T‐cell clonal expansion and effector function; whereas it promotes antigen‐driven responses during acute infection by positively regulating interferon signaling in T cells, PTPN22 inhibits homeostatic‐driven proliferation.