title: Protein tyrosine phosphatase PTPN22 has dual roles in promoting pathogen versus homeostatic-driven CD8 T-cell responses.
abstract: 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.
authors.affiliation: Division of Immunology Transplantation and Infectious Diseases (DITID), Diabetes Research Institute (DRI), IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Jofra
authors.affiliation: Division of Immunology Transplantation and Infectious Diseases (DITID), Diabetes Research Institute (DRI), IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Di Fonte
authors.affiliation: Department of Pathology, Immunology & Laboratory Medicine, University of Florida, Gainesville, FL, USA.
authors.forename: Tarun Edgar
authors.initials: TE
authors.lastname: Hutchinson
authors.affiliation: Department of Pathology, Immunology & Laboratory Medicine, University of Florida, Gainesville, FL, USA.
authors.forename: Farhad
authors.initials: F
authors.lastname: Dastmalchi
authors.affiliation: Division of Immunology Transplantation and Infectious Diseases (DITID), Diabetes Research Institute (DRI), IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Galvani
authors.affiliation: Division of Immunology Transplantation and Infectious Diseases (DITID), Diabetes Research Institute (DRI), IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Battaglia
authors.affiliation: Department of Pathology, Immunology & Laboratory Medicine, University of Florida, Gainesville, FL, USA.
authors.forename: Shahram
authors.initials: S
authors.lastname: Salek-Ardakani
authors.affiliation: Division of Immunology Transplantation and Infectious Diseases (DITID), Diabetes Research Institute (DRI), IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Georgia
authors.initials: G
authors.lastname: Fousteri
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D016207:Cytokines / Q000378:metabolism; D006706:Homeostasis; D007370:Interferon Type I / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D008216:Lymphocytic Choriomeningitis / Q000276:immunology / Q000821:virology; D008217:Lymphocytic choriomeningitis virus / Q000502:physiology*; D008810:Mice, Inbred C57BL; D010766:Phosphorylation; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22 / Q000172:deficiency / Q000378:metabolism*; D050794:STAT1 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; D016207:Cytokines; D007370:Interferon Type I; D050794:STAT1 Transcription Factor; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22; C516766:Ptpn22 protein, mouse