Role of Hedgehog signalling at the transition from double-positive to single-positive thymocyte
MetadataShow full item record
AbstractIn 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.
CitationFurmanski 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.
JournalEuropean Journal of Immunology
PubMed Central IDPMC3378705
The following license files are associated with this item:
- Creative Commons
Except where otherwise noted, this item's license is described as Yellow - can archive pre-print (ie pre-refereeing)
- Gli3 in fetal thymic epithelial cells promotes thymocyte positive selection and differentiation by repression of <i>Shh</i>.
- Authors: Solanki A, Yanez DC, Ross S, Lau CI, Papaioannou E, Li J, Saldaña JI, Crompton T
- Issue date: 2018 Jan 31
- Sonic Hedgehog regulates thymic epithelial cell differentiation.
- Authors: Saldaña JI, Solanki A, Lau CI, Sahni H, Ross S, Furmanski AL, Ono M, Holländer G, Crompton T
- Issue date: 2016 Apr
- The kinesin motor protein Kif7 is required for T-cell development and normal MHC expression on thymic epithelial cells (TEC) in the thymus.
- Authors: Lau CI, Barbarulo A, Solanki A, Saldaña JI, Crompton T
- Issue date: 2017 Apr 11
- Hedgehog signaling regulates differentiation from double-negative to double-positive thymocyte.
- Authors: Outram SV, Varas A, Pepicelli CV, Crompton T
- Issue date: 2000 Aug
- TCR signaling for initiation and completion of thymocyte positive selection has distinct requirements for ligand quality and presenting cell type.
- Authors: Yasutomo K, Lucas B, Germain RN
- Issue date: 2000 Sep 15