Flash Talk & Poster CD1-MR1 2024

Group A Streptococcus-induced CD1a-autoreactivity contributes to psoriasis (#233) (#44)

Yi-Ling Chen 1 2 , Jessica Soo Weei Ng 2 , Rosana Ottakandathil Babu 2 , Jeongmin Woo 2 , Janina Nahler 2 , Clare S Hardman 2 , Prathiba Kurupati 2 , Lea Nussbaum 2 , Fei Gao 1 , Tao Dong 1 2 , Kristin Ladell 3 , David A Price 3 , David A Duncan 4 , David Johnson 5 , Uzi Gileadi 2 , Hashem Koohy 2 , Graham S Ogg 2
  1. CAMS Oxford Institute, University of Oxford, Oxford, UK
  2. MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK
  3. Division of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, UK
  4. Diamond Light Source, Harwell Science and Innovation Campus, Didcot, UK.
  5. Department of Plastic and Reconstructive Surgery, John Radcliffe Hospital, Oxford University Hospitals National Health Services Foundation Trust, Oxford, UK

Group A Streptococcus (GAS) infection-associated immune disorders have been long known but how T cells are involved in their pathogenesis is largely unexplained. CD1a 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, a chronic inflammatory skin disease. 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. These GAS-responsive T cells were expanded and activated in patients with psoriasis, and can react to self-antigens, such as lysophosphatidylcholine (LPC). Furthermore, GAS infection in humanized CD1a transgenic mice drove an enhanced and prolonged 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.