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Ptpn2 and KLRG1 regulate the generation and function of tissue-resident memory CD8 + T cells in skin

Date

2021

Authors

Hochheiser, Katherina
Wiede, Florian
Wagner, Teagan
Freestone, David
Enders, Matthias H
Olshansky, Moshe
Russ, Brendan
Nüssing, Simone
Bawden, Emma
Braun, Asolina

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Journal ISSN

Volume Title

Publisher

Rockefeller University Press

Abstract

Tissue-resident memory T cells (T cells) are key elements of tissue immunity. Here, we investigated the role of the regulator of T cell receptor and cytokine signaling, Ptpn2, in the formation and function of T cells in skin. Ptpn2-deficient CD8 T cells displayed a marked defect in generating CD69 CD103 T cells in response to herpes simplex virus type 1 (HSV-1) skin infection. This was accompanied by a reduction in the proportion of KLRG1 memory precursor cells and a transcriptional bias toward terminal differentiation. Of note, forced expression of KLRG1 was sufficient to impede T cell formation. Normalizing memory precursor frequencies by transferring equal numbers of KLRG1− cells restored T generation, demonstrating that Ptpn2 impacted skin seeding with precursors rather than downstream T cell differentiation. Importantly, Ptpn2-deficient T cells augmented skin autoimmunity but also afforded superior protection from HSV-1 infection. Our results emphasize that KLRG1 repression is required for optimal T cell formation in skin and reveal an important role of Ptpn2 in regulating TRM cell functionality.

Description

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Citation

Source

Journal of Experimental Medicine

Type

Journal article

Book Title

Entity type

Access Statement

Open Access

License Rights

Creative Commons Attribution licence

DOI

10.1084/jem.20200940

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