IL10RA and colitis: While the studies outlined above demonstrate the critical role of IL10R signaling within MΦs in preventing inflammatory responses in the large intestine, the colitis that develops spontaneously in mice that are completely-deficient in IL10R or that specifically lack IL10R within CX3CR1+ MΦs manifest with a prolonged latency of several weeks, and is strain- and microbiota-dependent (Kang et al., 2008; Kühn et al., 1993; Spencer et al., 1998; Zigmond et al., 2014).