'We now provide compelling evidence that in hypoxic conditions, an autocrine IL-24/IL-24-receptor signaling/STAT3 loop is induced, which then sustains the HIF1α-mediated expression of epidermal IL-24. In turn, IL-24 acts in an autocrine and paracrine fashion to coordinate re-epithelialization, re-vascularization, dermal fibroblast proliferation, and collagen deposition to restore the damaged tissue to homeostasis.'
Liu, @mucida, Fuchs et al
@mucida The paper also has a very interesting evolutionary scenario
"Unbiased phylogenetic analyses indicated that this family and its receptors28 share greater sequence/structure homology to IFN and IFN-receptors than other cytokines/cytokine-receptors (Figures S1A and S1B; Table S3). Notably, the heterodimeric receptor subunits of the IFN and IL-10 families also sub-clustered, suggestive of a common ancestral heterodimeric receptor specific to these two families (Figure S1B). In contrast to IFNs, however, the IL-10 cytokine family has not been as clearly linked to pathogens/danger signals. This raises the tantalizing possibility that, during evolution, these pathways may have bifurcated from a common ancestor to cope with the increasing diversity of pathogens and injuries."
@gpollara @mucida @halama_immuno One thing that seems specific about the IL24 in this paper is that it is acting in a paracrine and/or autocrine manner. So this could be a dominant local regenerative response regardless of a broader pattern in other sites.
@cyrilpedia @gpollara @mucida And it also may be the link between #interferons , IL-10 and IL-1 bringing innate and adaptive #immunity together ...and very precise to point out the epidermal vs dermal compartimentalization @gpollara
@gpollara @cyrilpedia @mucida Is absolutely intriguing... maybe #monocytes are compartimentalized in a way that the differential IL-24 profile can associated... #immunology
@cyrilpedia
What an interesting paper, thank you for sharing.
The data and experiments look very solid. One comment - fig 1c is doing quite a lot of the heavy lifting in showing the specific induction of IL-24. Looks fair but how often is an injury just epidermis deep? If you get dermal injury, then IL-1b looks almost as specific a cytokine induced. Anyway, that's a separate story. IL-24 as an important local skin danger signal, I'm sold.
@mucida @halama_immuno