{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T06:34:12Z","timestamp":1773902052355,"version":"3.50.1"},"reference-count":20,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2016,10,11]],"date-time":"2016-10-11T00:00:00Z","timestamp":1476144000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000901","name":"Juvenile Diabetes Research Foundation International","doi-asserted-by":"publisher","award":["1\u2010FAC\u20102016\u2010144\u2010A\u2010N"],"award-info":[{"award-number":["1\u2010FAC\u20102016\u2010144\u2010A\u2010N"]}],"id":[{"id":"10.13039\/100000901","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AI087734"],"award-info":[{"award-number":["AI087734"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Immunol Cell Biol"],"published-print":{"date-parts":[[2017,2]]},"abstract":"<jats:p><jats:italic>PTPN22<\/jats:italic> (protein tyrosine phosphatase non receptor 22) encodes a tyrosine phosphatase that functions as a key regulator of immune homeostasis. In particular, PTPN22 inhibits T\u2010cell receptor signaling and selectively promotes type I interferon responses in myeloid cells. To date, there is little information on the CD8 T\u2010cell\u2010intrinsic role of PTPN22 in response to a viral pathogen. We unexpectedly found that PTPN22\u2010deficient virus\u2010specific CD8 T cells failed to accumulate in wild\u2010type hosts after lymphocytic choriomeningitis virus infection. Lack of PTPN22 expression altered CD8 T\u2010cell activation and antiviral cytokine production, but did not significantly affect the composition of effector and memory cell precursors. Most significantly, <jats:italic>in vivo<\/jats:italic>, PTPN22\u2010deficient CD8 T cells showed a profound defect in upregulating STAT\u20101 after lymphocytic choriomeningitis virus infection and considerably less phosphorylation of STAT\u20101 in response to IFN\u2010\u03b1 treatment <jats:italic>in vitro<\/jats:italic> compared with their wild\u2010type counterparts. In stark contrast, following transfer into lymphopenic mice, CD8 T\u2010cell expansion and central\u2010like phenotype, was considerably increased in the absence of PTPN22. Collectively, our results suggest that PTPN22 has dual roles in T\u2010cell clonal expansion and effector function; whereas it promotes antigen\u2010driven responses during acute infection by positively regulating interferon signaling in T cells, PTPN22 inhibits homeostatic\u2010driven proliferation.<\/jats:p>","DOI":"10.1038\/icb.2016.92","type":"journal-article","created":{"date-parts":[[2016,10,11]],"date-time":"2016-10-11T09:43:16Z","timestamp":1476178996000},"page":"121-128","source":"Crossref","is-referenced-by-count":15,"title":["Protein tyrosine phosphatase PTPN22 has dual roles in promoting pathogen versus homeostatic\u2010driven CD8 T\u2010cell responses"],"prefix":"10.1111","volume":"95","author":[{"given":"Tatiana","family":"Jofra","sequence":"first","affiliation":[{"name":"Division of Immunology Transplantation and Infectious Diseases (DITID), Diabetes Research Institute (DRI), IRCCS San Raffaele Scientific Institute  Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roberta","family":"Di Fonte","sequence":"additional","affiliation":[{"name":"Division of Immunology Transplantation and Infectious Diseases (DITID), Diabetes Research Institute (DRI), IRCCS San Raffaele Scientific Institute  Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tarun Edgar","family":"Hutchinson","sequence":"additional","affiliation":[{"name":"Department of Pathology, Immunology &amp; Laboratory Medicine, University of Florida  Gainesville FL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Farhad","family":"Dastmalchi","sequence":"additional","affiliation":[{"name":"Department of Pathology, Immunology &amp; Laboratory Medicine, University of Florida  Gainesville FL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giuseppe","family":"Galvani","sequence":"additional","affiliation":[{"name":"Division of Immunology Transplantation and Infectious Diseases (DITID), Diabetes Research Institute (DRI), IRCCS San Raffaele Scientific Institute  Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manuela","family":"Battaglia","sequence":"additional","affiliation":[{"name":"Division of Immunology Transplantation and Infectious Diseases (DITID), Diabetes Research Institute (DRI), IRCCS San Raffaele Scientific Institute  Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shahram","family":"Salek\u2010Ardakani","sequence":"additional","affiliation":[{"name":"Department of Pathology, Immunology &amp; Laboratory Medicine, University of Florida  Gainesville FL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Georgia","family":"Fousteri","sequence":"additional","affiliation":[{"name":"Division of Immunology Transplantation and Infectious Diseases (DITID), Diabetes Research Institute (DRI), IRCCS San Raffaele Scientific Institute  Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2016,10,11]]},"reference":[{"key":"e_1_2_5_1_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2014.109"},{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2013.10.006"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1403034"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.904"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI66963"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2013.06.013"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2014.12.002"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20050821"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.177.3.1746"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.176.8.4525"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1092138"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri853"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.174.6.3158"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2958"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.180.4.2158"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20142130"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/cei.12393"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2012.71"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20061462"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0077991"}],"container-title":["Immunology &amp; 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