02647nas a2200349   4500000000100000008004100001260001200042653001000054653002500064653001400089653001900103653001400122653002400136653001400160100001500174700001800189700001700207700001300224700001200237700001400249700001400263700001800277700001500295700001300310700001200323700001500335245010200350856008000452490000700532520174400539022001402283       2021                            d  c08/202110aIL-1510aMycobacterium leprae10aautophagy10aleprosy or T1R10alysosomes10amacrophage or THP-110aphagosome1 aSilva BJDA1 aBittencourt T1 aLeal-Calvo T1 aMendes M1 aPrata R1 aBarbosa M1 aAndrade P1 aCôrte-Real S1 ada Silva G1 aMoraes M1 aSarno E1 aPinheiro R00aAutophagy-Associated IL-15 Production Is Involved in the Pathogenesis of Leprosy Type 1 Reaction.  uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8468917/pdf/cells-10-02215.pdf0 v103 a<p>Leprosy reactional episodes are acute inflammatory events that may occur during the clinical course of the disease. Type 1 reaction (T1R) is associated with an increase in neural damage, and the understanding of the molecular pathways related to T1R onset is pivotal for the development of strategies that may effectively control the reaction. Interferon-gamma (IFN-) is a key cytokine associated with T1R onset and is also associated with autophagy induction. Here, we evaluated the modulation of the autophagy pathway in -stimulated cells in the presence or absence of IFN-. We observed that IFN- treatment promoted autophagy activation and increased the expression of genes related to the formation of phagosomes, autophagy regulation and function, or lysosomal pathways in -stimulated cells. IFN- increased interleukin (IL)-15 secretion in -stimulated THP-1 cells in a process associated with autophagy activation. We also observed higher  gene expression in multibacillary (MB) patients who later developed T1R during clinical follow-up when compared to MB patients who did not develop the episode. By overlapping gene expression patterns, we observed 13 common elements shared between T1R skin lesion cells and THP-1 cells stimulated with both  and IFN-. Among these genes, the autophagy regulator Translocated Promoter Region, Nuclear Basket Protein () was significantly increased in T1R cells when compared with non-reactional MB cells. Overall, our results indicate that IFN- may induce a TPR-mediated autophagy transcriptional program in -stimulated cells similar to that observed in skin cells during T1R by a pathway that involves IL-15 production, suggesting the involvement of this cytokine in the pathogenesis of T1R.</p>  a2073-4409