Abstract
Group 2 innate lymphoid cells (ILC2s) are tissue resident in the lung and activated by inhaled allergens via epithelial-derived alarmins including IL-33. Activated ILC2s proliferate, produce IL-5 and IL-13, and induce eosinophilic inflammation. Here, we report that intranasal IL-33 or the protease allergen papain administration resulted in increased numbers of ILC2s not only in the lung but also in peripheral blood and liver. Analyses of IL-33 treated parabiosis mice showed that the increase in lung ILC2s was due to proliferation of lung resident ILC2s, whereas the increase in liver ILC2s was due to the migration of activated lung ILC2s. Lung-derived ILC2s induced eosinophilic hepatitis and expression of fibrosis-related genes. Intranasal IL-33 pre-treatment also attenuated concanavalin A-induced acute hepatitis and cirrhosis. These results suggest that activated lung resident ILC2s emigrate from the lung, circulate, settle in the liver and promote type 2 inflammation and attenuate type 1 inflammation.
Highlights
Group 2 innate lymphoid cells (ILC2s) have been identified in mucosal and non-mucosal tissues, including the gut [1,2,3], lung [4], skin [5], adipose tissues [6, 7] and the liver [8]
We have previously shown that i.n. administrations of the protease allergen papain induce IL-33-dependent activation of lung ILC2s and increases in ILC2 numbers in the lung and in the draining mediastinal lymph node (LN) [20], suggesting that activated lung ILC2s might migrate out of the lung and enter the lymphatic system
C57BL/6J (B6), B6.SJL-PtprcaPepcb/BoyJ (Pep3b) and B6.129P2 (Cg)-Rorctm2Litt/J (Rorc-/-) mice were bred in the British Columbia Cancer Research Centre (BCCRC) and Biomedical Research Centre (BRC) animal facilities from breeder mice purchased from the Jackson Laboratory, and CD127 cKO mice were generated in house
Summary
Group 2 innate lymphoid cells (ILC2s) have been identified in mucosal and non-mucosal tissues, including the gut [1,2,3], lung [4], skin [5], adipose tissues [6, 7] and the liver [8]. They do not express T, B or myeloid cell lineage markers (Lin-), but express IL-7R (CD127) and CD90 (Thy1) [1,2,3]. ILC2s have been demonstrated to play key roles in papain [4], house dust mite [4, 18], ovalbumin
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