Elevated IL‐23 in skin promotes IL‐23 derived Th17 responses in leprosy patients

Abstract

Leprosy is an infectious disease caused by non-cultivable bacteria Mycobacterium leprae. Th17 cells play vital roles during pathogenesis of leprosy reactions and IL-23 is involved in Th17 cell differentiation. Although previous studies have reported the participation of IL-23 in leprosy patients in peripheral blood, the role of this cytokine in skin has not yet been described for the disease. In this study, we first evaluated IL-23 expression in the skin of patients with leprosy. Data showed that in keratinocytes, endothelial cells, and macrophages, IL-23 expression was markedly higher in patients compared to that in the normal skin controls. Also, leprosy patients presented higher percentage of IL-17A-producing IL-23R + CD4 T cells than healthy donors. IL-23R blocking induced markedly downregulated IL-17A secretion in leprosy patients but not in healthy donors. Furthermore, TGF-β expression was significantly elevated after IL-23R blocking. Overall, this study establishes that Th17 cells produce IL-17A in an IL-23 dependent manner in the skin of leprosy patients and provides more focused treatment strategies for Mycobacterium leprae.

Th17 Cells and Cytokines in Leprosy: Understanding the Immune Response and Polarization

“…In BL, Th17 cells play a protective role in the immune response 13,22 secreting IFN-γ, IL-4 and IL-5 13 . Conflicting data concerning IL-17 levels have been reported, suggesting decreased levels in the serum of patients with leprosy 23,24 , whereas other studies 13,14,17,25 have reported higher levels in the TT/BT polar forms than in the LL form [11][12][13][14]25,26 .…”

“…The cytokine IL-23 is secreted by keratinocytes, epithelial cells, and macrophages, and has been found in higher levels in patients with TT compared with those with LL, but at lower levels than those in healthy controls 13 , 22 . Blocking the signaling of rIL-23 in vitro in CD4+ T cells has been reported to decrease IL-17A production, increase TGF-β levels, and have minimal effect on IFN-γ and FoxP3 levels 22 .…”