Open AccessIL-33 Receptor-Expressing Regulatory T Cells Are Highly Activated, Th2 Biased and Suppress CD4 T Cell Proliferation through IL-10 and TGFβ Release
Author(s) -
Julia Siede,
Andreas Fröhlich,
Angeliki Datsi,
Ahmed N. Hegazy,
Domonkos V. Varga,
Vivien Holecska,
Hirohisa Saito,
Susumu Nakae,
Max Löhning
Publication year - 2016
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0161507
Subject(s) - foxp3 , homing (biology) , microbiology and biotechnology , chemokine , receptor , immunology , biology , chemokine receptor , t cell , population , inflammation , immune system , medicine , ecology , biochemistry , environmental health
Immunomodulatory Foxp3 + regulatory T cells (Tregs) form a heterogeneous population consisting of subsets with different activation states, migratory properties and suppressive functions. Recently, expression of the IL-33 receptor ST2 was shown on Tregs in inflammatory settings. Here we report that ST2 expression identifies highly activated Tregs in mice even under homeostatic conditions. ST2 + Tregs preferentially accumulate at non-lymphoid sites, likely mediated by their high expression of several chemokine receptors facilitating tissue homing. ST2 + Tregs exhibit a Th2-biased character, expressing GATA-3 and producing the Th2 cytokines IL-5 and IL-13 –especially in response to IL-33. Yet, IL-33 is dispensable for the generation and maintenance of these cells in vivo . Furthermore, ST2 + Tregs are superior to ST2 − Tregs in suppressing CD4 + T cell proliferation in vitro independent of IL-33. This higher suppressive capacity is partially mediated by enhanced production and activation of the anti-inflammatory cytokines IL-10 and TGFβ. Thus, ST2 expression identifies a highly activated, strongly suppressive Treg subset preferentially located in non-lymphoid tissues. Here ST2 + Tregs may be well positioned to immediately react to IL-33 alarm signals. Their specific properties may render ST2 + Tregs useful targets for immunomodulatory therapies.