title: 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-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 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-1β 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.
authors.affiliation: Department of Pediatrics I, University of Tübingen, Tübingen, Germany.
authors.forename: Marlene
authors.initials: M
authors.lastname: Ballbach
authors.forename: Tobias
authors.initials: T
authors.lastname: Hall
authors.forename: Alina
authors.initials: A
authors.lastname: Brand
authors.forename: Davide
authors.initials: D
authors.lastname: Neri
authors.forename: Anurag
authors.initials: A
authors.lastname: Singh
authors.forename: Iris
authors.initials: I
authors.lastname: Schaefer
authors.forename: Eva
authors.initials: E
authors.lastname: Herrmann
authors.forename: Sandra
authors.initials: S
authors.lastname: Hansmann
authors.forename: Rupert
authors.initials: R
authors.lastname: Handgretinger
authors.forename: Jasmin
authors.initials: J
authors.lastname: Kuemmerle-Deschner
authors.forename: Dominik
authors.initials: D
authors.lastname: Hartl
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Rieber
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000067531:Alarmins / Q000378:metabolism; D015551:Autoimmunity; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D056587:Cryopyrin-Associated Periodic Syndromes / Q000235:genetics / Q000276:immunology*; D005260:Female; D006801:Humans; D007108:Immune Tolerance; D007113:Immunity, Innate; D058847:Inflammasomes / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D000072737:Myeloid-Derived Suppressor Cells / Q000276:immunology*; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000235:genetics; D018417:Th1 Cells / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*; D055815:Young Adult
chemical_list: D000067531:Alarmins; D058847:Inflammasomes; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human