01951nas a2200181   4500000000100000008004100001100001200042700002000054700001200074700001000086700001300096700001200109700001400121245006200135856007700197520148100274022001401755       2015                            d1 aTeles R1 aKelly-Scumpia K1 aSarno E1 aRea T1 aOchoa MT1 aCheng G1 aModlin RL00aIL-27 Suppresses Antimicrobial Activity in Human Leprosy.  uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4567935/pdf/nihms693312.pdf3 a<p>The mechanisms by which intracellular pathogens trigger immunosuppressive pathways are critical for understanding the pathogenesis of microbial infection. One pathway that inhibits host defense responses involves the induction of type I interferons and subsequently IL-10, yet the mechanism by which type I IFN induces IL-10 remains unclear. Our studies of gene expression profiles derived from leprosy skin lesions suggested a link between IL-27 and the IFN-β induced IL-10 pathway. Here, we demonstrate that the IL-27p28 subunit is upregulated following treatment of monocytes with IFN-β and Mycobacterium leprae, the intracellular bacterium that causes leprosy. The ability of IFN-β and M. leprae to induce IL-10 was diminished by IL-27 knockdown. Additionally, treatment of monocytes with recombinant IL-27 was sufficient to induce the production of IL-10. Functionally, IL-27 inhibited the ability of IFN-γ to trigger antimicrobial activity against M. leprae in infected monocytes. At the site of disease, IL-27 was more strongly expressed in skin lesions of patients with progressive lepromatous leprosy, correlating and colocalizing with IFN-β and IL-10 in macrophages. Together, these data provide evidence that in the human cutaneous immune responses to microbial infection, IL-27 contributes to the suppression of host antimicrobial responses.Journal of Investigative Dermatology accepted article preview online, 01 June 2015. doi:10.1038/jid.2015.195.</p>
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