Late stages of T cell maturation in the thymus involve NF-?B and tonic type I interferon signaling.

ABSTRACT: Positive selection occurs in the thymic cortex, but critical maturation events occur later in the medulla. Here we defined the precise stage at which T cells acquired competence to proliferate and emigrate. Transcriptome analysis of late gene changes suggested roles for the transcription factor NF-?B and interferon signaling. Mice lacking the inhibitor of NF-?B (I?B) kinase (IKK) kinase TAK1 underwent normal positive selection but exhibited a specific block in functional maturation. NF-?B signaling provided protection from death mediated by the cytokine TNF and was required for proliferation and emigration. The interferon signature was independent of NF-?B; however, thymocytes deficient in the interferon-? (IFN-?) receptor IFN-?R showed reduced expression of the transcription factor STAT1 and phenotypic abnormality but were able to proliferate. Thus, both NF-?B and tonic interferon signals are involved in the final maturation of thymocytes into naive T cells.

SUBMITTER: Xing Y 

PROVIDER: S-EPMC4837029 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature