The choice of the second paper that I will present in 2013 is equally as important as the first one, and funnily once again it is a paper that follows one of the best presentations at ECI in Glasgow (see meeting report here – 06/10/2012).
The very challenging talk from Jessica Strid is indeed now available in Science!
She shows that combination of skin tape-stripping with epicutaneous antigen (ovalbumin) exposure leads to local and systemic Th2 response characterised by the production of ovalbumin-specific IgG1 and IgE. Moreover, IgE response is particularly dependent on the local skin induction of Rae-1 a ligand that is recognised by NKG2D that is expressed essentially on γδ T cells in the epithelium.
Therefore, the γδ T cell compartment has a profound effect on the production of antigen specific and total IgE after antigen exposure at mildly stressed epithelium. The γδ are required for the upregulation of IL-4, IL-13 and IL-25 mRNA in the epidermis. However, it remains to be formally demonstrated that they are the exclusive producers of these Th2-associated cytokines within the skin. Nevertheless, she went on to show that mice deficient in TCRVδ1Vγ5 that lack only the normal DETC repertoire are substantially impaired ovalbumin-specific and total IgE; as well as ovalabumin-dependent IL-13 production from skin-draining LN cells.
Do the DETC need to migrate to local skin-draining LN to influence the B cell response? Do they act indirectly merely by secreting the Th2-associated cytokines that will reach the LN microenvironment through the lymph? Do they act indirectly by “polarising” the langerhans cells and/or dendritic cells, within the epiderme, before they migrate to the skin-draining LN? This paper raises many questions, challenges our view on the link between and IgE γδ T cells, and thus is indeed a very interesting paper!!
In conclusion, I strongly recommend you all to have a look at these intriguing data “The intraepithelial T cell response to NKG2D-ligands links lymphoid stress surveillance to atopy”.