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

• Verfasst von: Orlik, Christian [VerfasserIn]
• Verfasst von: Berschneider, Karina M. [VerfasserIn]
• Verfasst von: Jahraus, Beate [VerfasserIn]
• Verfasst von: Niesler, Beate [VerfasserIn]
• Verfasst von: Balta, Emre [VerfasserIn]
• Verfasst von: Schäkel, Knut [VerfasserIn]
• Verfasst von: Schröder-Braunstein, Jutta [VerfasserIn]
• Verfasst von: Souto-Carneiro, Maria Margarida [VerfasserIn]
• Verfasst von: Samstag, Yvonne [VerfasserIn]
• Titel: Keratinocyte-induced costimulation of human T cells through CD6 - but not CD2 - activates mTOR and prevents oxidative stress
• Verf.angabe: Christian Orlik, Karina M. Berschneider, Beate Jahraus, Beate Niesler, Emre Balta, Knut Schäkel, Jutta Schröder-Braunstein, Maria Margarida Souto-Carneiro and Yvonne Samstag
• E-Jahr: 2022
• Jahr: 24 October 2022
• Umfang: 20 S.
• Fussnoten: Gesehen am 19.12.2022
• Titel Quelle: Enthalten in: Frontiers in immunology
• Ort Quelle: Lausanne : Frontiers Media, 2010
• Jahr Quelle: 2022
• Band/Heft Quelle: 13(2022), Artikel-ID 1016112, Seite 1-20
• ISSN Quelle: 1664-3224
• DOI: doi:10.3389/fimmu.2022.1016112
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1827901470
• K10plus-PPN:
  Universitätsbibliothek
• Lokale URL UB: Zum Volltext

Abstract

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.