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Previously, we used scRNA-Seq to characterize the cutaneous immune response in the EM lesion, focusing on B cells. Here, with an expanded sample size, we profiled T cell responses in EM lesions compared to autologous uninvolved skin. In addition to CD4\n                  <jats:sup>+<\/jats:sup>\n                  T cell subsets known to be abundant in the EM, we identified clonal expansion of CD8\n                  <jats:sup>+<\/jats:sup>\n                  GZMK\n                  <jats:sup>+<\/jats:sup>\n                  IFNG\n                  <jats:sup>+<\/jats:sup>\n                  T cells that exhibited significant differential expression of interferon-regulated genes. This subset included IFNG\n                  <jats:sup>+<\/jats:sup>\n                  cells with low cytotoxic gene expression, which may promote inflammation. While FOXP3\n                  <jats:sup>+<\/jats:sup>\n                  regulatory T cells were also increased in EM, they exhibited little IL10 expression. In contrast, a CD4\n                  <jats:sup>+<\/jats:sup>\n                  FOXP3\n                  <jats:sup>-<\/jats:sup>\n                  tissue-resident T cell subset contained the largest population of cells with IL10 expression. Fibroblasts, endothelial cells, and pericytes were the principal cells that significantly differentially expressed key T cell-recruiting chemokines. These studies represent the first comprehensive interrogation of the cutaneous T cell response to\n                  <jats:italic>Bb<\/jats:italic>\n                  infection using single cell transcriptomics with adaptive immune receptor sequencing, providing insight into the skin barrier defense and orchestration of the immune response to this vector-borne pathogen.\n                <\/jats:p>","DOI":"10.1101\/2025.06.09.658661","type":"posted-content","created":{"date-parts":[[2025,6,13]],"date-time":"2025-06-13T00:30:15Z","timestamp":1749774615000},"source":"Crossref","is-referenced-by-count":1,"title":["Single cell immunophenotyping identifies CD8\n                  <sup>+<\/sup>\n                  GZMK\n                  <sup>+<\/sup>\n                  IFNG\n                  <sup>+<\/sup>\n                  T cells as a key immune population in cutaneous Lyme disease"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8683-4772","authenticated-orcid":false,"given":"Edel","family":"Aron","sequence":"first","affiliation":[{"name":"Program in Computational Biology and Biomedical Informatics, Yale University, New Haven, Connecticut, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hailong","family":"Meng","sequence":"additional","affiliation":[{"name":"Department of Pathology, Yale School of Medicine, New Haven, Connecticut, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6784-7420","authenticated-orcid":false,"given":"Paraskevas","family":"Filippidis","sequence":"additional","affiliation":[{"name":"Department of Pathology, Yale School of Medicine, New Haven, Connecticut, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1734-8025","authenticated-orcid":false,"given":"Alexia A.","family":"Belperron","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4957-1544","authenticated-orcid":false,"given":"Steven H.","family":"Kleinstein","sequence":"additional","affiliation":[{"name":"Program in Computational Biology and Biomedical Informatics, Yale University, New Haven, Connecticut, USA"},{"name":"Department of Pathology, Yale School of Medicine, New Haven, Connecticut, USA"},{"name":"Department of Immunobiology, Yale School of Medicine, New Haven, Connecticut, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9349-8757","authenticated-orcid":false,"given":"Linda K.","family":"Bockenstedt","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026041203171063000_2025.06.09.658661v1.1","doi-asserted-by":"crossref","unstructured":"Steere AC , et al. 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