Activated mast cells produce soluble ST2-a decoy receptor for IL-33

Tuesday, September 23, 2014 — Poster Session III
12:00 p.m. – 2:00 p.m.	FAES Academic Center	NIAID	IMMUNO-1

Authors

• G. Bandara
• M.A. Beaven
• A. Olivera
• A.M. Gilfillan
• D.D. Metcalfe

Abstract

Interleukin (IL)-33, plays a central role in type 2 immune responses and inflammatory reactions in allergic and autoimmune diseases. IL-33 acts through its membrane bound receptor, ST2. A soluble spliced variant of ST2 (sST2) that lacks the ST2 cytosolic and transmembrane domains is thought to act as a decoy receptor to neutralize IL-33 activity. sST2 and IL-33 are elevated in many inflammatory diseases and serum levels of sST2 appear to correlate with disease severity. We investigated whether mast cells produce, and are a significant source of, sST2 during allergic reactions. We find that antigen and IL-33 evoke substantial release of sST2 from mouse and human mast cells and do so synergistically when added together or in combination with stem cell factor. Release of sST2 into circulation is also apparent during systemic anaphylaxis in mice. Human mast cells failed to generate IL-33 and IL-33 produced by mouse bone marrow-derived mast cells was retained within the cells. Therefore, it is unlikely that IL-33 acts in an autocrine manner to stimulate sST2 production. These results suggest that mast cells are a significant source of sST2 which may serve as a modulator of IL-33 activity and as a possible diagnostic marker in allergic diseases.

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