| First Author | Maxwell JR | Year | 2015 |
| Journal | Immunity | Volume | 43 |
| Issue | 4 | Pages | 739-50 |
| PubMed ID | 26431947 | Mgi Jnum | J:233770 |
| Mgi Id | MGI:5788043 | Doi | 10.1016/j.immuni.2015.08.019 |
| Citation | Maxwell JR, et al. (2015) Differential Roles for Interleukin-23 and Interleukin-17 in Intestinal Immunoregulation. Immunity 43(4):739-50 |
| abstractText | Interleukin-23 (IL-23) and IL-17 are cytokines currently being targeted in clinical trials. Although inhibition of both of these cytokines is effective for treating psoriasis, IL-12 and IL-23 p40 inhibition attenuates Crohn's disease, whereas IL-17A or IL-17 receptor A (IL-17RA) inhibition exacerbates Crohn's disease. This dichotomy between IL-23 and IL-17 was effectively modeled in the multidrug resistance-1a-ablated (Abcb1a(-/-)) mouse model of colitis. IL-23 inhibition attenuated disease by decreasing colonic inflammation while enhancing regulatory T (Treg) cell accumulation. Exacerbation of colitis by IL-17A or IL-17RA inhibition was associated with severe weakening of the intestinal epithelial barrier, culminating in increased colonic inflammation and accelerated mortality. These data show that IL-17A acts on intestinal epithelium to promote barrier function and provide insight into mechanisms underlying exacerbation of Crohn's disease when IL-17A or IL-17RA is inhibited. |
