Once again, I do not resist spreading some advertising. But this time it is not for me! It is for friends who are working in my previous institute – the MRC centre for Immune Regulation University of Birmingham in United Kingdom.
On top of that it is really funny since this is the first paper from the lab on γδ T cells!!!
The subject is on control of thymic T cell tolerance, and the question is: how is the tolerogenic micro-environment regulated?
It was previously shown that RANK signaling induced the expression of Aire (autoimmune regulator) in medullary thymic epithelial cells (mTECs).
This event is essential since Aire+ mTECs participate in T cell tolerance induction in several ways:
– negative selection of single-positive thymocytes that bear abTCRs recognizing tissue-restricted antigens
– development of FoxP3+ natural regulatory T cells
– intrathymic positioning of XCR1+ dendritic cells
In previous elegant studies, Prof G. Anderson’s group demonstrated that in the embryos the source of RANK signaling was provided by Lymphoid Tissue Inducer (LTi) cells Rossi et al., 2007 , while in the adult alpha/beta thymocytes were up for this task.
However, one challenging result came from the LTi-deficient Rorc-/-mice. Indeed, they found the presence of Aire+ mTECs in the developing embryonic thymus of mice lacking LTi at a stage prior to ab T cell selection White et al., 2008. This led to the hypothesis that additional embryonic cell types play a distinct role in establishing the medullary microenvironments to ensure T cell tolerance induction.
The present work is a follow up as they have now resolved this issue and found the missing piece of this puzzle! Indeed, the first appearance of Aire+ mTECs coincides with that of progenitors of Vγ5+ dendritic epidermal T cells (DETCs), a subset of invariant intraepithelial lymphocytes (IELs) whose development is uniquely linked to the embryonic thymus. They clearly show that DETC are an early source of RANK signaling in embryos.
Therefore, this is the first clear demonstration of a potential role of γδ T cells in shaping the thymic micro-environment previous to the first wave of ab thymocytes progenitors that colonise this organ! Thus, if you want to read more here is the link:
when rank is needed to stay in the rank!