| First Author | Fiancette R | Year | 2021 |
| Journal | Nat Immunol | Volume | 22 |
| Issue | 10 | Pages | 1245-1255 |
| PubMed ID | 34556884 | Mgi Jnum | J:320417 |
| Mgi Id | MGI:6874455 | Doi | 10.1038/s41590-021-01024-x |
| Citation | Fiancette R, et al. (2021) Reciprocal transcription factor networks govern tissue-resident ILC3 subset function and identity. Nat Immunol 22(10):1245-1255 |
| abstractText | Innate lymphoid cells (ILCs) are guardians of mucosal immunity, yet the transcriptional networks that support their function remain poorly understood. We used inducible combinatorial deletion of key transcription factors (TFs) required for ILC development (RORgammat, RORalpha and T-bet) to determine their necessity in maintaining ILC3 identity and function. Both RORgammat and RORalpha were required to preserve optimum effector functions; however, RORalpha was sufficient to support robust interleukin-22 production among the lymphoid tissue inducer (LTi)-like ILC3 subset, but not natural cytotoxicity receptor (NCR)(+) ILC3s. Lymphoid tissue inducer-like ILC3s persisted with only selective loss of phenotype and effector functions even after the loss of both TFs. In contrast, continued RORgammat expression was essential to restrain transcriptional networks associated with type 1 immunity within NCR(+) ILC3s, which coexpress T-bet. Full differentiation to an ILC1-like population required the additional loss of RORalpha. Together, these data demonstrate how TF networks integrate within mature ILCs after development to sustain effector functions, imprint phenotype and restrict alternative differentiation programs. |
