Induction of myeloid-derived suppressor cells in cryopyrin-associated periodic syndromes

Marlene Ballbach, Tobias Hall, Alina Brand, Davide Neri, Anurag Singh, Iris Schaefer, Eva Herrmann, Sandra Hansmann, Rupert Handgretinger, Jasmin Kuemmerle-Deschner, Dominik Hartl, Nikolaus Rieber

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

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.

Original languageEnglish
Pages (from-to)493-506
Number of pages14
JournalJournal of Innate Immunity
Volume8
Issue number5
DOIs
StatePublished - 1 Aug 2016
Externally publishedYes

Keywords

  • Autoinflammation
  • Chemokines
  • Cryopyrin-associated periodic syndrome
  • Growth factors
  • IL-1β
  • Myeloid-derived suppressor cells
  • NLRP3
  • Neutrophils

Fingerprint

Dive into the research topics of 'Induction of myeloid-derived suppressor cells in cryopyrin-associated periodic syndromes'. Together they form a unique fingerprint.

Cite this