02457nas a2200277   4500000000100000008004100001260001200042653001800054653000900072653001400081653001200095653001400107100001600121700001500137700001300152700001100165700001400176700001200190700001600202245010900218856007000327300001100397490000600408520175100414022001402165       2022                            d  c01/202210aT lymphocytes10aTreg10aCytokines10aleprosy10aReactions1 ade Castro K1 ada Silva P1 aSantos L1 aLeal J1 aPereira M1 aAlvim I1 aEsquenazi D00aDownmodulation of Regulatory T Cells Producing TGF-β Participates in Pathogenesis of Leprosy Reactions.  uhttps://www.frontiersin.org/articles/10.3389/fmed.2022.865330/pdf  a8653300 v93 a<p>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 and in response to (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 CD4TGF-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.</p>
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