Background: Unlike psoriasis and rheumatoid arthritis, anti-IL-17 therapy did not improve clinical outcomes in patients with Crohn's disease. We aimed to evaluate role of RORγt+ innate lymphoid cells (ILCs) in the chronic colitis under absence of IL-17.
Methods: To induce chronic colitis, CD4+CD45RBhi T cells of either wild-type (WT) C57BL/6 or Il17a-/- mice were transferred to Rag2-/- mice. Flow cytometry analysis was performed for analyzing RORγt+ ILCs in the colonic lamina propria of the chronic colitis model. Transcript expression was analyzed using the polymerase chain reaction.
Results: Body weight of Rag2-/- mice with T cell transfer from Il17a-/- mice was higher than that of Rag2-/- mice with T cell transfer from WT mice in early phase of colitis. At 9th week from the T cell transfer, however, body weights did not differ between the WT mice T cell transfer and Il17a-/- mice T cell transfer groups (81.9% vs. 82.2%; p=0.922). Intestinal inflammation score did not differ between two groups (p=0.494). Proportion of Lin-RORγt+ cells in lymphocytes was higher in the Il17a-/- mice T cell transfer group than in the WT mice T cell transfer group (22.6% vs. 16.8%). Proportion of Lin-CD4-RORγt+ cells was also slightly higher in the Il17a-/- mice T cell transfer (4.5% vs. 0.3%). Additionally, Il6, Il22, and Ifng were highly expressed in the Il17a-/- mice T cell transfer group.
Conclusions: IL-17A blockade could not attenuate chronic colitis. IL-17A blockade may induce increasing of ILC1s as well as RORγt+ ILCs, and eventually worsen chronic colitis.