Microbes and TNF drive colitis in the absence of innate lymphoid cells

Innate lymphoid cells (ILCs) are critical sources of cytokines necessary for intestinal homeostasis in immunocompetent conditions, yet their necessity in innate colitis remains unclear. Using a model of inflammatory bowel disease (IBD) in mice lacking adaptive immunity, we investigated whether ILCs are required for innate colitis. Interleukin-15 receptor alpha-deficient mice lacked intestinal ILC1 and natural killer (NK) cells, but innate colitis in these mice was not diminished. Deletion of IL-2 receptor gamma chain, which ablates all ILCs and NK cells, also did not prevent innate colitis. Antibiotic treatment of mice lacking all ILCs prevented colitis. Similarly, TNF deficiency prevented colitis in the absence of all ILCs, demonstrating that TNF is essential for microbe-driven innate colitis in the absence of ILCs. These findings reveal that ILCs are redundant for innate colitis. Studies of innate colitis in the absence of ILCs may help understand mechanisms underlying IBD and the effectiveness of anti-TNF therapies.