01781nas a2200217   4500000000100000008004100001260001200042100001200054700001700066700001400083700001200097700001300109700001300122700001300135245011500148856005500263300001000318490000700328520121400335022001401549       2020                            d  c09/20201 aSaini C1 aSrivastava R1 aTarique M1 aKurra S1 aKhanna N1 aRamesh V1 aSharma A00aElevated IL-6R on CD4 T cells promotes IL-6 driven Th17 cell responses in patients with T1R leprosy reactions.  uhttps://www.nature.com/articles/s41598-020-72148-7  a151430 v103 a<p>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-β 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 CD4IL6R T cells as compared to non-reaction (NR) patients. Furthermore, recombinant IL-6, IL-23 and TGF-β promoted IL-17A secretion by CD4IL6R 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-β and IL-23A may provide more focused treatment strategies for the management of Mycobacterium leprae and its reactions.</p>  a2045-2322