| First Author | Xing C | Year | 2021 |
| Journal | Cell Host Microbe | Volume | 29 |
| Issue | 6 | Pages | 959-974.e7 |
| PubMed ID | 33894128 | Mgi Jnum | J:320614 |
| Mgi Id | MGI:6874659 | Doi | 10.1016/j.chom.2021.03.016 |
| Citation | Xing C, et al. (2021) Microbiota regulate innate immune signaling and protective immunity against cancer. Cell Host Microbe 29(6):959-974.e7 |
| abstractText | Microbiota play critical roles in regulating colitis and colorectal cancer (CRC). However, it is unclear how the microbiota generate protective immunity against these disease states. Here, we find that loss of the innate and adaptive immune signaling molecule, TAK1, in myeloid cells (Tak1(DeltaM/DeltaM)) yields complete resistance to chemical-induced colitis and CRC through microbiome alterations that drive protective immunity. Tak1(DeltaM/DeltaM) mice exhibit altered microbiota that are critical for resistance, with antibiotic-mediated disruption ablating protection and Tak1(DeltaM/DeltaM) microbiota transfer conferring protection against colitis or CRC. The altered microbiota of Tak1(DeltaM/DeltaM) mice promote IL-1beta and IL-6 signaling pathways, which are required for induction of protective intestinal Th17 cells and resistance. Specifically, Odoribacter splanchnicus is abundant in Tak1(DeltaM/DeltaM) mice and sufficient to induce intestinal Th17 cell development and confer resistance against colitis and CRC in wild-type mice. These findings identify specific microbiota strains and immune mechanisms that protect against colitis and CRC. |
