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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]

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

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  • Media type: E-Article
  • Title: Keratinocyte-induced costimulation of human T cells through CD6 - but not CD2 - activates mTOR and prevents oxidative stress
  • Contributor: Orlik, Christian [VerfasserIn]; Berschneider, Karina M. [VerfasserIn]; Jahraus, Beate [VerfasserIn]; Niesler, Beate [VerfasserIn]; Balta, Emre [VerfasserIn]; Schäkel, Knut [VerfasserIn]; Schröder-Braunstein, Jutta [VerfasserIn]; Souto-Carneiro, Maria Margarida [VerfasserIn]; Samstag, Yvonne [VerfasserIn]
  • imprint: 24 October 2022
  • Published in: Frontiers in immunology ; 13(2022), Artikel-ID 1016112, Seite 1-20
  • Language: English
  • DOI: 10.3389/fimmu.2022.1016112
  • ISSN: 1664-3224
  • Identifier:
  • Origination:
  • Footnote:
  • Description: 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.
  • Access State: Open Access