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Keratinocyte-induced costimulation of human T cells through CD6 - but not CD2 - activates mTOR and prevents oxidative stress

In psoriasis and other inflammatory skin diseases, keratinocytes (KCs) secrete chemokines that attract T cells, which, in turn, cause epidermal hyperplasia by secreting proinflammatory cytokines. To date, it remains unclear whether skin-homing T cells, particularly memory T cells, can also be activa...

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Main Authors: Orlik, Christian (Author) , Berschneider, Karina M. (Author) , Jahraus, Beate (Author) , Niesler, Beate (Author) , Balta, Emre (Author) , Schäkel, Knut (Author) , Schröder-Braunstein, Jutta (Author) , Souto-Carneiro, Maria Margarida (Author) , Samstag, Yvonne (Author)
Format: Article (Journal)
Language:English
Published: 24 October 2022
In: Frontiers in immunology
Year: 2022, Volume: 13, Pages: 1-20
ISSN:1664-3224
DOI:10.3389/fimmu.2022.1016112
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.3389/fimmu.2022.1016112
Verlag, kostenfrei, Volltext: https://www.frontiersin.org/articles/10.3389/fimmu.2022.1016112
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Author Notes:Christian Orlik, Karina M. Berschneider, Beate Jahraus, Beate Niesler, Emre Balta, Knut Schäkel, Jutta Schröder-Braunstein, Maria Margarida Souto-Carneiro and Yvonne Samstag
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Summary:In psoriasis and other inflammatory skin diseases, keratinocytes (KCs) secrete chemokines that attract T cells, which, in turn, cause epidermal hyperplasia by secreting proinflammatory cytokines. To date, it remains unclear whether skin-homing T cells, particularly memory T cells, can also be activated by direct cell contact with KCs. In this study, we demonstrated the ability of primary human KCs to activate human memory T cells directly by transmitting costimulatory signals through the CD6/CD166/CD318 axis. Interestingly, despite being negative for CD80/CD86, KCs initiate a metabolic shift within T cells. Blockade of the CD6/CD166/CD318 axis prevents mammalian target of rapamycin activation and T cell proliferation but promotes oxidative stress and aerobic glycolysis. In addition, it diminishes formation of central memory T cells. Importantly, although KC-mediated costimulation by CD2/CD58 also activates T cells, it cannot compensate for the lack of CD6 costimulation. Therefore, KCs likely differentially regulate T cell functions in the skin through two distinct costimulatory receptors: CD6 and CD2. This may at least in part explain the divergent effects observed when treating inflammatory skin diseases with antibodies to CD6 versus CD2. Moreover, our findings may provide a molecular basis for selective interference with either CD6/CD166/CD318, or CD2/CD58, or both to specifically treat different types of inflammatory skin diseases.
Item Description:Gesehen am 19.12.2022
Physical Description:Online Resource
ISSN:1664-3224
DOI:10.3389/fimmu.2022.1016112

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