IL-33-mediated IL-13 secretion by ST2(+) Tregs controls inflammation after lung injury

Liu, Quan1,2,3; Dwyer, Gaelen K.1,4; Zhao, Yifei1,5; Li, Huihua6; Mathews, Lisa R.1; Chakka, Anish Bhaswanth7; Chandran, Uma R.7; Demetris, Jake A.1,8; Alcorn, John F.9; Robinson, Keven M.7; Ortiz, Luis A.10; Pitt, Bruce R.10; Thomson, Angus W.1,2,4; Fan, Ming-Hui6; Billiar, Timothy R.2; Turnquist, Heth R.1,2,4

2019-03-21

10.1172/jci.insight.123919

JCI Insight   影响因子和分区

2324-7703

2379-3708

Acute respiratory distress syndrome is an often fatal disease that develops after acute lung injury and trauma. How released tissue damage signals, or alarmins, orchestrate early inflammatory events is poorly understood. Herein we reveal that IL-33, an alarmin sequestered in the lung epithelium, is required to limit inflammation after injury due to an unappreciated capacity to mediate Foxp3(+) Treg control of local cytokines and myeloid populations. Specifically, Il33 (-1-) mice are more susceptible to lung damage-associated morbidity and mortality that is typified by augmented levels of the proinflammatory cytokines and Ly6C(hi) monocytes in the bronchoalveolar lavage fluid. Local delivery of IL-33 at the time of injury is protective but requires the presence of Treg cells. IL-33 stimulates both mouse and human Tregs to secrete IL-13. Using Foxp3(cre) x Il4/Il13(fl/fl) mice, we show that Treg expression of IL-13 is required to prevent mortality after acute lung injury by controlling local levels of G-CSF,IL-6, and MCP-1 and inhibiting accumulation of Ly6C(hi) monocytes. Our study identifies a regulatory mechanism involving IL-33 and Treg secretion of IL-13 in response to tissue damage that is instrumental in limiting local inflammatory responses and may shape the myeloid compartment after lung injury.

SCI

英语

其他

[P30CA047904]

Research & Experimental Medicine

Medicine, Research & Experimental

WOS:000463372800005

AMER SOC CLINICAL INVESTIGATION INC

Web of Science

1.Univ Pittsburgh, Sch Med, Thomas E Starzl Transplantat Inst, Pittsburgh, PA 15261 USA
2.Univ Pittsburgh, Sch Med, Dept Surg, Pittsburgh, PA 15261 USA
3.Southern Univ Sci & Technol, Sch Med, Shenzhen, Peoples R China
4.Univ Pittsburgh, Dept Immunol, Sch Med, Pittsburgh, PA 15261 USA
5.Tsinghua Univ, Sch Med, Beijing, Peoples R China
6.Univ Pittsburgh, Sch Med, Dept Med, Div Pulm Allergy & Crit Care Med, Pittsburgh, PA 15261 USA
7.Univ Pittsburgh, Sch Med, Dept Biomed Informat, Pittsburgh, PA 15261 USA
8.Univ Pittsburgh, Sch Med, Dept Pathol, Pittsburgh, PA 15261 USA
9.Univ Pittsburgh, Childrens Hosp Pittsburgh, Med Ctr, Dept Pediat, Pittsburgh, PA 15261 USA
10.Univ Pittsburgh, Grad Sch Publ Hlth, Dept Environm & Occupat Heath, Pittsburgh, PA 15261 USA

Liu, Quan,Dwyer, Gaelen K.,Zhao, Yifei,et al. IL-33-mediated IL-13 secretion by ST2(+) Tregs controls inflammation after lung injury[J]. JCI Insight,2019,4(6).

Liu, Quan.,Dwyer, Gaelen K..,Zhao, Yifei.,Li, Huihua.,Mathews, Lisa R..,...&Turnquist, Heth R..(2019).IL-33-mediated IL-13 secretion by ST2(+) Tregs controls inflammation after lung injury.JCI Insight,4(6).

Liu, Quan,et al."IL-33-mediated IL-13 secretion by ST2(+) Tregs controls inflammation after lung injury".JCI Insight 4.6(2019).