Mast cells as sensors of cell injury through IL-33 recognition.
In response to cell injury, caused, for example, by trauma, several processes must be initiated simultaneously to achieve an acute inflammatory response designed to prevent sustained tissue damage and infection and to restore and maintain tissue homeostasis. Detecting cell injury is facilitated by the fact that damaged cells release intracellular molecules not normally present in the extracellular space. However, potential underlying mechanisms for the recognition of endogenous danger signals released upon cell injury have yet to be elucidated. In this study, we demonstrate that mast cells, potent promoters of acute inflammation, play a key role in responding to cell injury by recognizing IL-33 released from necrotic structural cells. In an in vitro model of cell injury, this recognition was shown to involve the T1/ST2 receptor and result in the secretion of proinflammatory leukotrienes and cytokines by mouse mast cells. Remarkably, of all of the components released upon necrosis, our results show that IL-33 alone is a key component responsible for initiating proinflammatory responses in mast cells reacting to cell injury. Our findings identify IL-33 as a key danger signal released by necrotic structural cells capable of activating mast cells, thus providing novel insights concerning the role of mast cells as sensors of cell injury.
Clinical Immunology and Allergy Unit, Department of Medicine, Karolinska Institute, SE-171 76 Stockholm, Sweden.
Mattias
M
Enoksson
Katarina
K
Lyberg
Christine
C
Möller-Westerberg
Padraic G
PG
Fallon
Gunnar
G
Nilsson
Carolina
C
Lunderius-Andersson
D000818:Animals; D002474:Cell-Free System / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D007249:Inflammation / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D000067596:Interleukin-33; D007378:Interleukins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D015289:Leukotrienes / Q000378:metabolism; D008407:Mast Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009336:Necrosis
D016207:Cytokines; C506535:Il33 protein, mouse; D000067596:Interleukin-33; D007378:Interleukins; D015289:Leukotrienes