Serum factor regulation of mast cell desensitization following combined immunotherapy 2308953

Abstract Introduction Our laboratory recently developed cell culture systems allowing selective differentiation of MCs co-expressing tryptase and chymase (MCTC), similar to those residing in peripheral connective tissues, and expressing tryptase alone (MCT), the principal phenotype found in mucosal epithelium. Due to their in vivo location, MCT are likely central drivers of allergic responses in the airways and digestive tissues, but little is known about the differential sensitivity of each subset to both activation and desensitization. Methods To test this, we selectively differentiated MCT and MCTC from peripheral blood-derived CD34+ cells and sensitized them using patient serum samples from a recent study of cat allergic individuals evaluating effects of subcutaneous immunotherapy (SCIT), Tezepelumab (TEZE) treatment, or combined TEZE/SCIT. We then evaluated and compared MCT and MCTC activation via flow cytometry. Results Our findings indicated that MCT exhibit a striking increase in sensitivity to cat dander compared with MCTC. Both treatments in isolation lead to decreased MC activation, with TEZE limiting MC priming and SCIT limiting MC activation through blocking allergen recognition in an IgG-independent manner. Evaluation of the TEZE/SCIT group indicated that combined therapy leads to robust desensitization of both subsets to a greater degree than either therapy in isolation. Conclusion Use of combined therapies like TEZE/SCIT may provide necessary alternatives to more effectively target both MCT and MCTC. Funding Source NIH grant AI007306, Immune Tolerance Network, FASI Topic Categories Immediate Hypersensitivity, Asthma, and Allergic Responses (HYP)