ICOS promotes group 2 innate lymphoid cell activation in lungs.
Group 2 innate lymphoid cells (ILC2s) are newly identified, potent producers of type 2 cytokines, such as IL-5 and IL-13, and contribute to the development of allergic lung inflammation induced by cysteine proteases. Although it has been shown that inducible costimulator (ICOS), a costimulatory molecule, is expressed on ILC2s, the role of ICOS in ILC2 responses is largely unknown. In the present study, we investigated whether the interaction of ICOS with its ligand B7-related protein-1 (B7RP-1) can promote ILC2 activation. Cytokine production in ILC2s purified from mouse lungs was significantly increased by coculture with B7RP-1-transfected cells, and increased cytokine production was inhibited by monoclonal antibody-mediated blocking of the ICOS/B7RP-1 interaction. ILC2 expansion and eosinophil influx induced by papain, a cysteine protease antigen, in mouse lungs were significantly abrogated by blocking the ICOS/B7RP-1 interaction. Dendritic cells (DCs) in the lungs expressed B7RP-1 and the number of DCs markedly increased with papain administration. B7RP-1 expression on lung DCs was reduced after papain administration. This downregulation of B7RP-1 expression may be an indication of ICOS/B7RP-1 binding. These results indicate that ILC2s might interact with B7RP-1-expressing DCs in allergic inflammatory lung, and ICOS signaling can positively regulate the protease allergen-induced ILC2 activation followed by eosinophil infiltration into the lungs.
['Kamachi|Fumitaka|F|', 'Isshiki|Takuma|T|', 'Harada|Norihiro|N|', 'Akiba|Hisaya|H|', 'Miyake|Sachiko|S|']
D000818:Animals D005434:Flow Cytometry D007113:Immunity, Innate D060889:Inducible T-Cell Co-Stimulator Protein D008168:Lung D008297:Male D051379:Mice D008810:Mice, Inbred C57BL D010206:Papain
Group 2 innate lymphoid cell Allergic lung inflammation Inducible costimulator