Journal
INTERNATIONAL IMMUNOPHARMACOLOGY
Volume 122, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.intimp.2023.110631
Keywords
Mast cell; Skin; Psoriasis; Secretory leukocyte proteinase inhibitor; Chymase; IgE; Mrgprb2; MRGPRX2
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This study investigated the role of secretory leukocyte protease inhibitor (SLPI) in mast cell-dependent processes and found that SLPI inhibits the activity of chymase in mast cells and enhances their degranulation. The study also showed that SLPI is expressed in dermal mast cells of patients with psoriasis. These findings reveal previously unknown mechanisms underlying FceRI and Mrgprb2-dependent mast cell function.
Psoriasis, which involves mast cells, is a chronic inflammatory skin disorder whose pathophysiology is still not fully understood. We investigated the role of secretory leukocyte protease inhibitor (SLPI), a potential inhibitor of mastocyte serine proteases, on mast cell-dependent processes of relevance to the skin barrier defense in psoriasis. Here, we demonstrate that the dermal mast cells of patients with psoriasis express SLPI but not those of healthy donors. Moreover, SLPI transcripts were found to be markedly upregulated in murine mast cells by mediators derived from psoriasis skin explant cultures. Using mast cells from SLPI-deficient mice and their SLPI+ wild-type controls, we show that SLPI inhibits the activity of serine protease chymase in mastocytes. SLPI was also found to enhance the degranulation of mast cells activated via anti-IgE Abs but not Mrgprb2 ligands. Finally, we demonstrate that the expression and function of Mrgprb2 in mast cells are suppressed by a normal and, to a larger extent, psoriatic skin environment. Together, these findings reveal mechanisms underlying FceRI- and Mrgprb2-dependent mast cell function that have not been described previously.
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