PropertyValue
?: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.
is ?:annotates of
?:creator
?:doi
  • 10.3389/fimmu.2020.590964
?:doi
?:journal
  • Front_Immunol
?:license
  • cc-by
?:pdf_json_files
  • document_parses/pdf_json/5aa0ae05460da4d8afe0b0a0619a015ce7df908b.json
?:pmc_json_files
  • document_parses/pmc_json/PMC7592429.xml.json
?:pmcid
?:pmid
?:pmid
  • 33178223.0
?:publication_isRelatedTo_Disease
is ?:relation_isRelatedTo_publication of
?:sha_id
?:source
  • Medline; PMC
?:title
  • CD28 Autonomous Signaling Orchestrates IL-22 Expression and IL-22-Regulated Epithelial Barrier Functions in Human T Lymphocytes
?:type
?:year
  • 2020-10-14

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