Innate activation of Th17 cells triggers IL-26 release

Abstract

Abstract IL-26 is a Th17 cell cytokine with both pro-inflammatory effects and direct antimicrobial activity. We investigated the role of IL-26 in the host response to infection by studying leprosy as a model, finding that IL-26 had direct antimicrobial activity against Mycobacterium leprae. IL-26 mRNA and protein expression was greater in skin lesions from patients with self-limited versus progressive infection, although IL-17 was weakly expressed. To determine 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 suggesting activation of the innate response. IL-26 was secreted from PBMCs in response to a variety of pattern recognition receptor (PRR) ligands, correlating with IL-1β release. In PBMCs, IL-1β stimulated IL-26 secretion and blocking IL-1β with either antibodies or depletion of CD14+ cells after PRR ligand stimulation lead to reduction in IL-26 secretion. IL-1β also stimulated IL-26 secretion by both CD4+ and CD8+ T cells, and within the CD4+ compartment IL-26 secretion was limited to memory T cells. Only CD4+ memory Th17 cells, not Th1 or Th2, produced IL-26 in response to IL-1β, and expressed higher amounts of surface IL-1R1. Memory CD4+ T cells stimulated with IL-1β or αCD3/αCD28 secreted IL-26, but only cells stimulated with αCD3/αCD28 secreted IL-17 and IFN-γ. These studies suggest that Th17 cells play a role in the innate immune response by selectively secreting the antibacterial and pro-inflammatory cytokine IL-26 in response to IL-1β.