Downmodulation of Regulatory T Cells Producing TGF-β Participates in Pathogenesis of Leprosy Reactions.

Autor:	Gomes de Castro KK; Leprosy Laboratory, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil., Lopes da Silva PH; Leprosy Laboratory, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil., Nahar Dos Santos L; Leprosy Laboratory, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil., Leal JMP; Leprosy Laboratory, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil., de Pinho Pereira MM; Leprosy Laboratory, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil., Alvim IMP; Leprosy Laboratory, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil., Esquenazi D; Leprosy Laboratory, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.; Department of Pathology and Laboratories, School of Medical Sciences, State University of Rio de Janeiro, Rio de Janeiro, Brazil.
Jazyk:	angličtina
Zdroj:	Frontiers in medicine [Front Med (Lausanne)] 2022 Jul 18; Vol. 9, pp. 865330. Date of Electronic Publication: 2022 Jul 18 (Print Publication: 2022).
DOI:	10.3389/fmed.2022.865330
Abstrakt:	Leprosy reactions are an acute and systemic manifestation, which occurs suddenly, can be severe and lead leprosy patients to disability. Reactional episodes are observed among half of the multibacillary patients, mainly in borderline lepromatous and lepromatous forms. They may begin at any time during multidrug therapy, and even before the treatment. Physical disabilities, which are the source of extreme suffering and pain for patients, occur in progression of the cellular immune response associated with a reaction and are still poorly understood. Thus, this work aimed to phenotypically and functionally characterize CD4 + and CD8 + Treg cells ex vivo and in response to Mycobacterium leprae (ML). We studied 52 individuals, including 18 newly diagnosed and untreated multibacillary leprosy patients, 19 reactional multibacillary patients (Type I or Type II episodes) and 15 healthy volunteers, included as controls, all residents of the city of Rio de Janeiro. The functional activity and frequencies of these cells were evaluated through multiparametric flow cytometry. In addition, the production of cytokines in supernatant from peripheral blood mononuclear cell cultures was also investigated against ML by enzyme-linked immunosorbent assay. Our results showed a decrease in CD4 + TGF-β + Treg and CD8 + TGF-β + Treg in leprosy multibacillary patients during both types of reactional episodes. Alterations in the cytokine profile was also observed in Type II reactions, along with upregulation of IL-17 and IL-6 in supernatant. Thus, our study suggests that downregulation of Treg cells is related with both classes of reactional episodes, improving our understanding of immune hyporesponsiveness in multibacillary patients and hyperesponsiveness in both reactions. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Gomes de Castro, Lopes da Silva, Nahar dos Santos, Leal, de Pinho Pereira, Alvim and Esquenazi.)
Databáze:	MEDLINE
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