IL-22 is a member of the IL-10 cytokine family involved in host protection against extracellular pathogens, by promoting epithelial cell regeneration and barrier functions. Dysregulation of IL-22 production has also frequently been observed in acute respiratory distress syndrome (ARDS) and several chronic inflammatory and autoimmune diseases. We have previously described that human CD28, a crucial co-stimulatory receptor necessary for full T cell activation, is also able to act as a TCR independent signaling receptor and to induce the expression of IL-17A and inflammatory cytokines related to Th17 cells, which together with Th22 cells represent the main cellular source of IL-22. Here we characterized the role of CD28 autonomous signaling in regulating IL-22 expression in human CD4+ T cells. We show that CD28 stimulation in the absence of TCR strongly up-regulates IL-22 gene expression and secretion. As recently observed for IL-17A, we also found that CD28-mediated regulation of IL-22 transcription requires the cooperative activities of both IL-6-activated STAT3 and RelA/NF-κB transcription factors. CD28-mediated IL-22 production also promotes the barrier functions of epithelial cells by inducing mucin and metalloproteases expression. Finally, by using specific inhibitory drugs, we also identified CD28-associated class 1A phosphatidylinositol 3-kinase (PI3K) as a pivotal mediator of CD28-mediated IL-22 expression and IL-22–dependent epithelial cell barrier functions.

CD28 autonomous signaling orchestrates IL-22 expression and IL-22-regulated epithelial barrier functions in human T lymphocytes / Kunkl, M.; Amormino, C.; Frascolla, S.; Sambucci, M.; De Bardi, M.; Caristi, S.; Arcieri, S.; Battistini, L.; Tuosto, L.. - In: FRONTIERS IN IMMUNOLOGY. - ISSN 1664-3224. - 11:14(2020). [10.3389/fimmu.2020.590964]

CD28 autonomous signaling orchestrates IL-22 expression and IL-22-regulated epithelial barrier functions in human T lymphocytes

Kunkl M.
Primo
;
Amormino C.;Caristi S.;Arcieri S.;Tuosto L.
2020

Abstract

IL-22 is a member of the IL-10 cytokine family involved in host protection against extracellular pathogens, by promoting epithelial cell regeneration and barrier functions. Dysregulation of IL-22 production has also frequently been observed in acute respiratory distress syndrome (ARDS) and several chronic inflammatory and autoimmune diseases. We have previously described that human CD28, a crucial co-stimulatory receptor necessary for full T cell activation, is also able to act as a TCR independent signaling receptor and to induce the expression of IL-17A and inflammatory cytokines related to Th17 cells, which together with Th22 cells represent the main cellular source of IL-22. Here we characterized the role of CD28 autonomous signaling in regulating IL-22 expression in human CD4+ T cells. We show that CD28 stimulation in the absence of TCR strongly up-regulates IL-22 gene expression and secretion. As recently observed for IL-17A, we also found that CD28-mediated regulation of IL-22 transcription requires the cooperative activities of both IL-6-activated STAT3 and RelA/NF-κB transcription factors. CD28-mediated IL-22 production also promotes the barrier functions of epithelial cells by inducing mucin and metalloproteases expression. Finally, by using specific inhibitory drugs, we also identified CD28-associated class 1A phosphatidylinositol 3-kinase (PI3K) as a pivotal mediator of CD28-mediated IL-22 expression and IL-22–dependent epithelial cell barrier functions.
2020
CD28; epithelial cell; IL-22; inflammation; T cell
01 Pubblicazione su rivista::01a Articolo in rivista
CD28 autonomous signaling orchestrates IL-22 expression and IL-22-regulated epithelial barrier functions in human T lymphocytes / Kunkl, M.; Amormino, C.; Frascolla, S.; Sambucci, M.; De Bardi, M.; Caristi, S.; Arcieri, S.; Battistini, L.; Tuosto, L.. - In: FRONTIERS IN IMMUNOLOGY. - ISSN 1664-3224. - 11:14(2020). [10.3389/fimmu.2020.590964]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1456992
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