Skin-resident memory T cells mediate delayed-onset drug hypersensitivity reactions in human and mice
Final Report Abstract
In this prospective study we collected skin and blood pre- and post-SCT from multiple patients. For n= 3 patients and a total of 12 specimens (4 samples per patient), we successfully established single cell suspensions and performed single cell RNA sequencing (scRNAseq) with T cell receptor sequencing and single nucleotide polymorphism (snp) analysis to assess host (and donor) T cells post-SCT to proof the concept of a novel avenue researching SCT and GvHD. By including pre-SCT skin and blood samples in prospective study sampling, TCR sequencing was able to identify whether host T cells in skin post-SCT derived from host skin pre-SCT (presumably TRM) or migrated into the skin from blood following SCT. We observed in our prospectively collected clinical samples that the majority of T cells in skin at 30 days post-SCT were host, while comparatively the majority of T cells in blood were donor-derived using TCR sequencing. In addition, our pipeline was able to identify the origin, activation and function of non-T cells (NK cells, APCs) that may likewise contribute to GvHD. Future plans for this project is to apply the established pipeline in a larger prospective clinical studies to track these cell populations over time in patients post-SCT and in the development of GVHD for which we submitted an R01 grant based on our proof of concept study. We are also currently finalizing the analysis of our data with the goal to submit a research manuscript to Blood.
Publications
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“Donor-derived T cells accumulate in skin during resolution of acute GvHD” July 2020, Journal of Investigative Dermatology – SID 2020 Meeting Abstract Supplement
Khatib L, Schunkert EM, Hsieh PC, Divito SJ
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“Immunologic profiling of fixed drug eruptions” July 2020, Journal of Investigative Dermatology – SID 2020 Meeting Abstract Supplement
Schunkert EM, Romar GA, Hsieh PC, Foreman RK, Barrera Burgos V, Divito SJ
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“Role of Skin TRM in mediating delayed-onset drug hypersensitivity reactions” August 2021, Frontiers in Immunology
Schunkert EM, Shah PN, Divito SJ
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“Updates and Insights in the Diagnosis and Management of DRESS Syndrome” September 2021, Springer’s Current Dermatology Reports (PMID: 34777921)
Schunkert EM, Divito SJ
