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DYSREGULATED ILC3S-ILCREGS AXIS IN TYPE 1 REACTIONS (T1R) OF LEPROSY

Abstract

Introduction: Leprosy Type 1 Reaction (T1R) is a chronic inflammatory disorder involving dysregulation between T helper cells, particularly Th17 and Tregs, has been postulated in earlier investigations to be responsible for T1R responses. ILCs (innate lymphoid cells) are predominantly present in the skin and are known to modulate Th17 and Tregs cells. Thus, understanding the pathogenic involvement of ILCs in T1R would offer fresh perspective on the intervention and therapy of T1R reactions.

Methods: The study included 20 T1R and 20 non-reaction (NR) patients. By using flowcytometry, we identified both ILC3s and ILCregs, in the MLSA stimulated PBMCs. In-situ skin gene expression of cytokines (IL-17A and TGF-β) was further examined using qPCR.

Findings: T1R had significantly (p<0.0001) higher percentages of CD3-CD19- CCR6+IL17A+ (ILC3s) as compared with non-reaction patients. Of interest T1R showed significantly (p<0.0002) lower percentages of TGF-β producing CD3- CD25+CD127+FOXP3- than in NR patients. Surprisingly, CD3-CD25+CD127+FOXP3- (ILCregs) cells had no significant difference between T1R and NR patients. Moreover, IL-17 expression was significantly high in T1R skin lesions as compared to NR patients. On other hand, TGF-β was significantly low in skin of T1R as compared to NR patients.

Discussion: A dysregulation between Th17 and Tregs has been postulated in our early investigations to be responsible for T1R responses initially activated by ILCs. In this study, we have reported that ILC3s were significantly high in T1R and ILCregs were downregulated in T1R. As ILCs are predominantly present in the skin. Moreover, IL-17A gene expression was also upregulated in T1R skin lesions. Thus, present approaches spacificaly targate Th17 cells that may provide more focused treatment strategies for leprosy reactions.

Conclusion: In this study, leprosy T1R reactions showed dysregulated “ILC3s- ILCreg” cell balance as compared to non-reaction (NR) patients. Collectively our data for the first time report the role of ILCs in pathophysiology of T1R in Leprosy.

More information

Type
Journal Article
Author
Saini C
Sapra L
Bhardwaj A
Tarique M
Sharma A
Ramesh V
Puri P
Srivastava R

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