Innate lymphoid cells and colitis in leukocyte adhesion deficiency

• Published in: The Journal of immunology (1950) 2017-05, Vol.198 (1_Supplement), p.200-200.9
• Main Authors: Wang, Baomei, Li, Xiaofei, Kajikawa, Tetsuhiro, Moutsopoulos, Niki M, Chavakis, Triantafyllos, Hajishengallis, George
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.198.Supp.200.9

Leukocyte Adhesion Deficiency type I (LAD-I) is a primary immune deficiency caused by mutations in the CD18 subunit of β2 integrins. Affected individuals suffer from recurrent mucocutaneous infections and pathologic inflammation in certain mucosal barriers, including the periodontium, skin and the colon. Our laboratory has recently dissected the mechanistic basis of LAD-I–associated periodontitis but the mechanisms underlying LAD-I– associated colitis are yet to be defined. To answer this question, we utilized as model the CD18−/− mice after demonstrated that CD18 deficiency renders mice highly susceptible to Citrobacter rodentium-induced colitis, a widely used model of human colitis caused by enteropathogenic and enterohaemorrhagic Escherichia coli. Strikingly, we found that CD18−/− mice displayed significantly reduced IL-22 production and IL-22 producing Group 3 innate lymphoid cells (ILC3s). Therapeutic delivery of recombinant IL-22 (rIL-22) protected CD18−/− mice from C. rodentium–induced mortality. Furthermore, adoptive transfer of CD18+/+ monocytes partially restored IL-22 production from ILC3s and extended the survival of CD18−/− mice post C. rodentium infection. This is the first demonstration that ILC3-dependent expression of IL-22 is under β2 integrin regulation. In conclusion, these data not only identified a novel role of β2 integrin in mediating the crosstalk between intestinal macrophage and ILC3 but also can potentially lead to novel treatment of LAD-associated colitis.