Online Poster Portal

  • Author
    David Weiss
  • Co-author

    Feiyang Ma, Matteo Pellegrini, Robert Modlin

  • Title

    Human antimicrobial Th17 cells produce IL-26 in response to IL-1β

  • Abstract

    Th17 cells play a fundamental role in both immunity and autoimmunity at mucosal surfaces, including skin. Recent work has implicated the Th17 cytokine IL-26 as both directly antimicrobial to extracellular and intracellular bacteria, including Mycobacterium leprae, the causative agent of leprosy. IL-26 protein expression was greater in skin lesions from patients with the resistant vs. progressive form of the disease. To understand the mechanism for IL-26 induction, we examined the kinetics of IL-26 secretion by PBMCs exposed to Mycobacterium leprae sonicate, which revealed induction at 3 hours, reminiscent of an innate response. Pattern recognition receptor ligands induced IL-26 secretion from PBMC, which was mediated by IL-1β. Recombinant IL-1β alone was sufficient to stimulate IL-26 release from PBMC and memory CD4+ T cells in the absence of T cell receptor (TCR) activation. IL-1β stimulated IL-26 secretion more rapidly from memory CD4+ T cells as compared to TCR activation with crosslinking antibodies. Further investigation revealed that the majority of IL-1b induced IL-26 was form memory Th17 cells that expressed IL-1R1, and not from Th1 or Th2 cells.  IL-1β stimulation did not lead to secretion of other Th17 cytokines, unlike TCR activation.  RNA sequencing of IL-1β treated IL-1RI+ Th17 cells revealed enrichment for NF-κB regulated genes. Inhibition of NF-κB signaling with Bay 11-7082 abrogated IL-26 production in response to either stimulus.  Finally, supernatants from IL-1β treated memory T cells showed antimicrobial activity against E.  coli in an IL-26 dependent manner.  Together, these results identify IL-1RI+ Th17 cells as an antimicrobial Th17 subpopulation with the ability to rapidly respond to IL-1β and induce IL-26 to kill extracellular bacteria.

  • College

    AAC

  • Zoom

    https://uclahs.zoom.us/j/93853207007

  • PDF

    pdf_image