Protein tyrosine phosphatase PTPN22 has dual roles in promoting pathogen versus homeostatic-driven CD8 T-cell responses

T Jofra, Roberta Di Fonte, TE Hutchinson, F Dastmalchi, Giuseppe Galvani, M Battaglia, S Salek-Ardakani, G Fousteri

Research output: Contribution to journalArticle

6 Citations (Scopus)

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.Immunology and Cell Biology advance online publication, 11 October 2016; doi:10.1038/icb.2016.92. © 2016 Australasian Society for Immunology Inc.
Original languageEnglish
Pages (from-to)121-128
Number of pages8
JournalImmunology and Cell Biology
Volume95
Issue number2
DOIs
Publication statusPublished - 2017

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Non-Receptor Protein Tyrosine Phosphatases
Protein Tyrosine Phosphatases
T-Lymphocytes
Lymphocytic choriomeningitis virus
Virus Diseases
Allergy and Immunology
Non-Receptor Type 2 Protein Tyrosine Phosphatase
Interferon Type I
Myeloid Cells
T-Cell Antigen Receptor
Phosphoric Monoester Hydrolases
Interferons
Antiviral Agents
Cell Biology
Tyrosine
Publications
Homeostasis
Phosphorylation

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Protein tyrosine phosphatase PTPN22 has dual roles in promoting pathogen versus homeostatic-driven CD8 T-cell responses. / Jofra, T; Di Fonte, Roberta; Hutchinson, TE; Dastmalchi, F; Galvani, Giuseppe; Battaglia, M; Salek-Ardakani, S; Fousteri, G.

In: Immunology and Cell Biology, Vol. 95, No. 2, 2017, p. 121-128.

Research output: Contribution to journalArticle

Jofra, T, Di Fonte, R, Hutchinson, TE, Dastmalchi, F, Galvani, G, Battaglia, M, Salek-Ardakani, S & Fousteri, G 2017, 'Protein tyrosine phosphatase PTPN22 has dual roles in promoting pathogen versus homeostatic-driven CD8 T-cell responses', Immunology and Cell Biology, vol. 95, no. 2, pp. 121-128. https://doi.org/10.1038/icb.2016.92
Jofra, T ; Di Fonte, Roberta ; Hutchinson, TE ; Dastmalchi, F ; Galvani, Giuseppe ; Battaglia, M ; Salek-Ardakani, S ; Fousteri, G. / Protein tyrosine phosphatase PTPN22 has dual roles in promoting pathogen versus homeostatic-driven CD8 T-cell responses. In: Immunology and Cell Biology. 2017 ; Vol. 95, No. 2. pp. 121-128.
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