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Induction of Myeloid-Derived Suppressor Cells in Cryopyrin-Associated Periodic Syndromes.


ABSTRACT: Cryopyrin-associated periodic syndromes (CAPS) are caused by mutations in the NLRP3 gene leading to overproduction of IL-1? and other NLRP3 inflammasome products. Myeloid-derived suppressor cells (MDSCs) represent a novel innate immune cell subset capable of suppressing T-cell responses. As inflammasome products were previously found to induce MDSCs, we hypothesized that NLRP3 inflammasome-dependent factors induce the generation of MDSCs in CAPS. We studied neutrophilic MDSCs, their clinical relevance, and MDSC-inducing factors in a unique cohort of CAPS patients under anti-IL-1 therapy. Despite anti-IL-1 therapy and low clinical disease activity, CAPS patients showed significantly elevated MDSCs compared to healthy controls. MDSCs were functionally competent, as they suppressed polyclonal T-cell proliferation, as well as Th1 and Th17 responses. In addition, MDSCs decreased monocytic IL-1? secretion. Multiplex assays revealed a distinct pattern of MDSC-inducing cytokines, chemokines, and growth factors. Experimental analyses demonstrated that IL-1 cytokine family members and autoinflammation-associated alarmins differentially induced human MDSCs. Increased MDSCs might represent a novel autologous anti-inflammatory mechanism in autoinflammatory conditions and may serve as a future therapeutic target.

SUBMITTER: Ballbach M 

PROVIDER: S-EPMC6743338 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Induction of Myeloid-Derived Suppressor Cells in Cryopyrin-Associated Periodic Syndromes.

Ballbach Marlene M   Hall Tobias T   Brand Alina A   Neri Davide D   Singh Anurag A   Schaefer Iris I   Herrmann Eva E   Hansmann Sandra S   Handgretinger Rupert R   Kuemmerle-Deschner Jasmin J   Hartl Dominik D   Rieber Nikolaus N  

Journal of innate immunity 20160629 5


Cryopyrin-associated periodic syndromes (CAPS) are caused by mutations in the NLRP3 gene leading to overproduction of IL-1β and other NLRP3 inflammasome products. Myeloid-derived suppressor cells (MDSCs) represent a novel innate immune cell subset capable of suppressing T-cell responses. As inflammasome products were previously found to induce MDSCs, we hypothesized that NLRP3 inflammasome-dependent factors induce the generation of MDSCs in CAPS. We studied neutrophilic MDSCs, their clinical rel  ...[more]

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