Figure 8. Schematic summary: MC immuno-phenotype and MC-CD8+ T-cell interactions in healthy compared to lesional AA skin.

In human healthy skin, MCs are mostly non-degranulated and they express the SCF receptor, c-Kit, and MHCI molecules. Most of them express IL-10, TGFβ1 while only some express OX40L and PD-L1 and very few express CD30L and ICAM-1 (A). In lesional AA skin, the degranulation of MCs is increased (release of tryptase, heparin and histamine) and the expression of tryptase is increased, while the contents of TGFbeta1, IL-10 are decreased. Moreover, the numbers of OX40L+, CD30L+, 4-1BBL+ and ICAM-1+ MCs are up-regulated, while MCs positive for IL-10 and PD-L1 are down-regulated (B). In human healthy skin, rare MCs are found in close contact with CD8+ T-cells and most of them express OX40L. Therefore, we hypothesized that OX40/OX40L might mediate this interaction. Rarely, we found IL-10+ MCs interacting with CD8+ T-cells (C). In lesional AA skin, many MCs interact with CD8+ T-cells. During this cross-talk, most MCs express OX40L but instead, in some rare cases, 4-1BBL and ICAM-1 were expressed. These ligands might stimulate the activation and proliferation of CD8+ T-cells. Since MCs during the interaction are also degranulating, we hypothesize an activation of PAR-2 (tryptase receptor) on CD8+ T-cells. Finally, we suggest that MCs may operate as autoantigen-presenting cells (D). This schematic drawing was prepared using the Biomedical-PPT-Toolkit-Suite of Motifolio Inc., USA.