Helper-type innate lymphoid cells(ILC)play an important role in intestinal homeostasis.Members of the NKR-P1 gene family are expressed in various innate immune cells,including natural killer(NK)cells,and their cognate...Helper-type innate lymphoid cells(ILC)play an important role in intestinal homeostasis.Members of the NKR-P1 gene family are expressed in various innate immune cells,including natural killer(NK)cells,and their cognate Clr ligand family members are expressed in various specialized tissues,including the intestinal epithelium,where they may play an important role in mucosalassociated innate immune responses.In this study,we show that the inhibitory NKR-P1B receptor,but not the Ly49 receptor,is expressed in gut-resident NK cells,ILC,and a subset ofγδT cells in a tissue-specific manner.ILC3 cells constitute the predominant cell subset expressing NKR-P1B in the gut lamina propria.The known NKR-P1B ligand Clr-b is broadly expressed in gut-associated cells of hematopoietic origin.The genetic deletion of NKR-P1B results in a higher frequency and number of ILC3 andγδT cells in the gut lamina propria.However,the function of gut-resident ILC3,NK,andγδT cells in NKR-P1B-deficient mice is impaired during gastrointestinal tract infection by Citrobacter rodentium or Salmonella typhimurium,resulting in increased systemic bacterial dissemination in NKR-P1B-deficient mice.Our findings highlight the role of the NKR-P1B:Clr-b recognition system in the modulation of intestinal innate immune cell functions.展开更多
基金supported by Operating Grants from the Canadian Institutes of Health Research(CIHR 86630 to A.P.M.and J.R.C.and CIHR 388337 to A.M.).
文摘Helper-type innate lymphoid cells(ILC)play an important role in intestinal homeostasis.Members of the NKR-P1 gene family are expressed in various innate immune cells,including natural killer(NK)cells,and their cognate Clr ligand family members are expressed in various specialized tissues,including the intestinal epithelium,where they may play an important role in mucosalassociated innate immune responses.In this study,we show that the inhibitory NKR-P1B receptor,but not the Ly49 receptor,is expressed in gut-resident NK cells,ILC,and a subset ofγδT cells in a tissue-specific manner.ILC3 cells constitute the predominant cell subset expressing NKR-P1B in the gut lamina propria.The known NKR-P1B ligand Clr-b is broadly expressed in gut-associated cells of hematopoietic origin.The genetic deletion of NKR-P1B results in a higher frequency and number of ILC3 andγδT cells in the gut lamina propria.However,the function of gut-resident ILC3,NK,andγδT cells in NKR-P1B-deficient mice is impaired during gastrointestinal tract infection by Citrobacter rodentium or Salmonella typhimurium,resulting in increased systemic bacterial dissemination in NKR-P1B-deficient mice.Our findings highlight the role of the NKR-P1B:Clr-b recognition system in the modulation of intestinal innate immune cell functions.
