Group A Streptococcus induces CD1a-autoreactive T cells and promotes psoriatic inflammation

Chen, Yi-Ling, Ng, Jessica Soo Weei, Ottakandathil Babu, Rosana, Woo, Jeongmin, Nahler, Janina, Hardman, Clare S., Kurupati, Prathiba, Nussbaum, Lea, Gao, Fei, Dong, Tao, Ladell, Kristin ORCID: https://orcid.org/0000-0002-9856-2938, Price, David A. ORCID: https://orcid.org/0000-0001-9416-2737, Duncan, David A., Johnson, David, Gileadi, Uzi, Koohy, Hashem and Ogg, Graham S. 2023. Group A Streptococcus induces CD1a-autoreactive T cells and promotes psoriatic inflammation. Science Immunology 8 (84) , eadd9232. 10.1126/sciimmunol.add9232

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Abstract

Group A Streptococcus (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+ and CD8+ 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+ 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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Publisher:	American Association for the Advancement of Science
ISSN:	2470-9468
Date of First Compliant Deposit:	26 July 2023
Date of Acceptance:	26 April 2023
Last Modified:	06 Nov 2023 17:33
URI:	https://orca.cardiff.ac.uk/id/eprint/161270

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