Hairless mouse Hr mutation induces skin commensal bacterial changes and skin mastocytosis

We observed that Hairless (Hr-/-) mice skin has an aberrant expression of chymase and trypsin-like activity that correlated with the accumulation of mast cells (MCs) in their dermis (skin mastocytosis). The accumulation of MCs in Hr-/- mice corresponded to an increased release of MC mediators when the mice were stimulated with 48/80, a Mrgx MC specific degranulation agent, indicating that MCs were functional and mature.To understand the underlying pathogenesis of Hr-/- mastocytosis, we investigated both intrinsic and extrinsic factors that could lead to the excessive number of MCs present in the hairless skin including: vitamin D receptor (VDR) pathway, commensal composition and stem cell factor (SCF) expression in the skin of Hr-/- mice compared to their littermates. Given that Hr gene has been reported to be disruptive in the VDR pathway, 1,25-Dihydroxyvitamin D (VD) i.p. injections were performed onto Hr-/- and their littermates; however, no changes were noticed in MC number after VD i.p. injections. KIT and its ligand, SCF are essential elements for the mast cell development. KIT mutations (that lead to constitutive activation) are commonly detected in patients with mastocytosis. Moreover, previous studies from our lab demonstrated that MC maturation and migrationcan be determined by skin commensal gram-positive bacteria through the TLR2-SCF pathway. Interestingly, when we analyzed the skin microbiome composition on WT and Hr-/- mice, we found that Hr-/- mouse skin contained a lower amount of bacteria, but that bacteria composition presented with a higher ratio of gram-positive bacteria than in WT mice. Compatible with these results, compared to wild type littermate mice, hairless mice had higher lipoteichoic (LTA) in the epidermis (quantified by immunofluorescence), ligand of Toll-like receptor 2 (TLR2), and also higher expression of SCF along skin epidermis. Our study reveals that the hairless gene changes the mouse skin structure leading to a different skin commensal bacteria population, higher SCF expression in the skin and also mastocytosis.