Elevated IL-6R on CD4+ T cells promotes IL-6 driven Th17 cell responses in patients with T1R leprosy reactions

Th17 cells play vital role during pathogenesis of leprosy reactions. Previously, we have reported that IL-23 is involved in Th17 cells differentiation. Subsequently, our group also showed that IL-6 induces Th17 cell differentiation along with TGF-beta in leprosy reactions. Here, we next asked the question that whether IL-6 or IL-23 induced Th17 cells are different in nature? In this study, Type 1 Reactions (T1R) showed significantly (p<0.001) higher percentage of IL-17A producing CD4(+)IL6R(+) T cells as compared to non-reaction (NR) patients. Furthermore, recombinant IL-6, IL-23 and TGF-<beta> promoted IL-17A secretion by CD4(+)IL6R(+) T cells. Subsequently, IL-6R and IL-23R blocking experiments showed significantly (p<0.002) down regulated IL-17A in T1R reaction as compared to NR leprosy patients. The present study for the first time establishes that pathogenic Th17 cells produce IL-17 in an IL-6 dependent manner in leprosy T1R reactions. Thus, present approaches that specifically target Th17 cells and/or the cytokines that promote their development, such as IL-6, TGF-<beta> and IL-23A may provide more focused treatment strategies for the management of Mycobacterium leprae and its reactions.