Role of Hedgehog signalling at the transition from double-positive to single-positive thymocyte
Abstract
In the thymus, developing T cells receive signals that determine lineage choice, specificity, MHC restriction and tolerance to self‐antigen. One way in which thymocytes receive instruction is by secretion of Sonic hedgehog (Shh) from thymic epithelial cells. We have previously shown that Hedgehog (Hh) signalling in the thymus decreases the CD4:CD8 single‐positive (SP) thymocyte ratio. Here, we present data indicating that double‐positive (DP) thymocytes are Hh‐responsive and that thymocyte‐intrinsic Hh signalling plays a role in modulating the production of CD4+ (SP4), CD8+ (SP8) and unconventional T‐cell subsets. Repression of physiological Hh signalling in thymocytes altered the proportions of DP and SP4 cells. Thymocyte‐intrinsic Hh‐dependent transcription also attenuated both the production of mature SP4 and SP8 cells, and the establishment of peripheral T‐cell compartments in TCR‐transgenic mice. Additionally, stimulation or withdrawal of Hh signals in the WT foetal thymus impaired or enhanced upregulation of the CD4 lineage‐specific transcription factor Gata3 respectively. These data together suggest that Hh signalling may play a role in influencing the later stages of thymocyte development.Citation
Furmanski AL, Saldana JI, Rowbotham NJ, Ross SE, Crompton T (2012) 'Role of Hedgehog signalling at the transition from double-positive to single-positive thymocyte', European Journal of Immunology, 42 (2), pp.489-499.Publisher
WileyJournal
European Journal of ImmunologyPubMed ID
22101858PubMed Central ID
PMC3378705Additional Links
https://onlinelibrary.wiley.com/doi/full/10.1002/eji.201141758Type
ArticleLanguage
enISSN
0014-2980ae974a485f413a2113503eed53cd6c53
10.1002/eji.201141758
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