Abstract
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 CD4+IL6R+ T cells as compared to non-reaction (NR) patients. Furthermore, recombinant IL-6, IL-23 and TGF-β 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-β and IL-23A may provide more focused treatment strategies for the management of Mycobacterium leprae and its reactions.
Highlights
Type 1 reaction (T1R) of leprosy can develop acute episodes of inflammation leading to severe morbidity, nerve damage and irreversible disability
To validate whether enhanced IL-6 receptor (IL-6R) expression on CD4+ T cells is causative of elevated IL-17A response in Type 1 Reactions (T1R) leprosy patients, we studied the effect of blocking of IL-6R and IL-23R in Mycobacterium leprae sonicated antigen (MLSA) induced IL-17A production by peripheral blood mononuclear cells (PBMCs) cells in-vitro
Our earlier study Saini et al.[8] showed that when T helper cells polarization is not occurring against M. leprae antigen, Th17 cells play a protective role in stable leprosy (NR) patients
Summary
Type 1 reaction (T1R) of leprosy can develop acute episodes of inflammation leading to severe morbidity, nerve damage and irreversible disability. Isolated CD4+ T helper cells were investigated in 19 of each Type 1 reactions (T1R) patients and non-reactions (NR) leprosy patients by Real Time PCR (qPCR) for RNA estimation.
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