{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Chen YL"],"funding":["Medical Research Council","National Institute for Health Research (NIHR)","Wellcome Trust"],"pagination":["eadd9232"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC7615662"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["8(84)"],"pubmed_abstract":["Group A <i>Streptococcus</i> (GAS) infection is associated with multiple clinical sequelae, including different subtypes of psoriasis. Such post-streptococcal disorders have been long known but are largely unexplained. CD1a is expressed at constitutively high levels by Langerhans cells and presents lipid antigens to T cells, but the potential relevance to GAS infection has not been studied. Here, we investigated whether GAS-responsive CD1a-restricted T cells contribute to the pathogenesis of psoriasis. Healthy individuals had high frequencies of circulating and cutaneous GAS-responsive CD4<sup>+</sup> and CD8<sup>+</sup> T cells with rapid effector functions, including the production of interleukin-22 (IL-22). Human skin and blood single-cell CITE-seq analyses of IL-22-producing T cells showed a type 17 signature with proliferative potential, whereas IFN-γ-producing T cells displayed cytotoxic T lymphocyte characteristics. Furthermore, individuals with psoriasis had significantly higher frequencies of circulating GAS-reactive T cells, enriched for markers of activation, cytolytic potential, and tissue association. In addition to responding to GAS, subsets of expanded GAS-reactive T cell clones/lines were found to be autoreactive, which included the recognition of the self-lipid antigen lysophosphatidylcholine. CD8<sup>+</sup> T cell clones/lines produced cytolytic mediators and lysed infected CD1a-expressing cells. Furthermore, we established cutaneous models of GAS infection in a humanized CD1a transgenic mouse model and identified enhanced and prolonged local and systemic inflammation, with resolution through a psoriasis-like phenotype. Together, these findings link GAS infection to the CD1a pathway and show that GAS infection promotes the proliferation and activation of CD1a-autoreactive T cells, with relevance to post-streptococcal disease, including the pathogenesis and treatment of psoriasis."],"journal":["Science immunology"],"pubmed_title":["Group A &lt;i&gt;Streptococcus&lt;/i&gt; induces CD1a-autoreactive T cells and promotes psoriatic inflammation."],"pmcid":["PMC7615662"],"funding_grant_id":["MC_UU_00036/2","100326/Z/12/Z","MC_UU_00036/5","MC_UU_00008","MC_UU_00008/6","MC_UU_00008/5","209222/Z/17/Z","NIHR203691"],"pubmed_authors":["Dong T","Price DA","Nussbaum L","Gao F","Koohy H","Ng JSW","Ogg GS","Hardman CS","Kurupati P","Gileadi U","Duncan DA","Johnson D","Ottakandathil Babu R","Ladell K","Chen YL","Woo J","Nahler J"],"additional_accession":[]},"is_claimable":false,"name":"Group A &lt;i&gt;Streptococcus&lt;/i&gt; induces CD1a-autoreactive T cells and promotes psoriatic inflammation.","description":"Group A <i>Streptococcus</i> (GAS) infection is associated with multiple clinical sequelae, including different subtypes of psoriasis. Such post-streptococcal disorders have been long known but are largely unexplained. CD1a is expressed at constitutively high levels by Langerhans cells and presents lipid antigens to T cells, but the potential relevance to GAS infection has not been studied. Here, we investigated whether GAS-responsive CD1a-restricted T cells contribute to the pathogenesis of psoriasis. Healthy individuals had high frequencies of circulating and cutaneous GAS-responsive CD4<sup>+</sup> and CD8<sup>+</sup> T cells with rapid effector functions, including the production of interleukin-22 (IL-22). Human skin and blood single-cell CITE-seq analyses of IL-22-producing T cells showed a type 17 signature with proliferative potential, whereas IFN-γ-producing T cells displayed cytotoxic T lymphocyte characteristics. Furthermore, individuals with psoriasis had significantly higher frequencies of circulating GAS-reactive T cells, enriched for markers of activation, cytolytic potential, and tissue association. In addition to responding to GAS, subsets of expanded GAS-reactive T cell clones/lines were found to be autoreactive, which included the recognition of the self-lipid antigen lysophosphatidylcholine. CD8<sup>+</sup> T cell clones/lines produced cytolytic mediators and lysed infected CD1a-expressing cells. Furthermore, we established cutaneous models of GAS infection in a humanized CD1a transgenic mouse model and identified enhanced and prolonged local and systemic inflammation, with resolution through a psoriasis-like phenotype. Together, these findings link GAS infection to the CD1a pathway and show that GAS infection promotes the proliferation and activation of CD1a-autoreactive T cells, with relevance to post-streptococcal disease, including the pathogenesis and treatment of psoriasis.","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Jun","modification":"2026-06-10T09:23:32.368Z","creation":"2025-04-04T07:49:00.988Z"},"accession":"S-EPMC7615662","cross_references":{"pubmed":["37267382"],"doi":["10.1126/sciimmunol.add9232"]}}