Glycome remodeling programs pathogenic γδ T17 cell responses in autoimmunity
Glycans play fundamental roles in T cell biology; however, the glycome landscape of γδ T cells remains to be unlocked. Despite the growing importance of γδ T cells in host defense, tissue homeostasis, and diseases, the glycosylation mechanisms guiding their activation, commitment, and function remain poorly defined. By performing single-cell RNA sequencing, we revealed that type 3/γδ T17/interleukin-17A (IL-17A)–committed γδ T cells rely on ( N-acetylglucosaminyltransferase 1 ) MGAT1 – MGAT5 –mediated branched N-glycosylation. We further demonstrated that the absence of branched N -glycans on γδ T cells acts as a peripheral signal, driving an IL-17A–pro-inflammatory phenotype, alongside a shift to a Vγ4 + subset and the imprinting of innate-like properties. This altered glycoform of type 3 γδ T cells was shown to induce severe psoriasis. γδ T cells from patients with autoimmune and inflammatory diseases exhibited a deficiency in branched N -glycans. Glycan supplementation can reprogram γδ T cells toward a less-pathogenic state, highlighting N -glycans as a previously unrecognized immune checkpoint for γδ T cells.
Authors
- Lyndsay E.A. Young (ORCID: https://orcid.org/0000-0002-6873-5674)
- Carlos Vasconcelos (ORCID: https://orcid.org/0000-0002-8073-5028)
- Ana Campar (ORCID: https://orcid.org/0000-0002-3951-8961)
- Yohannes Tafesse (ORCID: https://orcid.org/0000-0003-3883-6244)
- Beatriz Santos‐Pereira (ORCID: https://orcid.org/0000-0002-7094-0394)
- David Vermijlen (ORCID: https://orcid.org/0000-0002-7605-8845)
- Richard R. Drake (ORCID: https://orcid.org/0000-0002-6285-6440)
- António Marinho (ORCID: https://orcid.org/0000-0002-3295-6723)
- Salomé S. Pinho (ORCID: https://orcid.org/0000-0002-3484-5162)
- Daniela Santos Oliveira (ORCID: https://orcid.org/0000-0001-9734-3162)
- Ana Maria Lé (ORCID: https://orcid.org/0000-0002-3559-0413)
- Bruno Cavadas (ORCID: https://orcid.org/0000-0003-4104-5398)
- Guillem Sanchez Sanchez (ORCID: https://orcid.org/0000-0001-9919-1748)
- Joana Torres (ORCID: https://orcid.org/0000-0003-2895-5821)
- José Delgado Alves (ORCID: https://orcid.org/0000-0002-5216-4125)
- Tiago Torres (ORCID: https://orcid.org/0000-0003-0404-0870)
- Eduarda Leite-Gomes (ORCID: https://orcid.org/0000-0002-5541-4759)
- Inês Alves (ORCID: https://orcid.org/0000-0002-3914-7101)
- Rafaela Nogueira (ORCID: https://orcid.org/0009-0009-3788-0121)
- Ariana Correia‐Silva (ORCID: https://orcid.org/0000-0002-9355-7806)
- João F. Serodio
- Xavier Luppens (ORCID: https://orcid.org/0009-0006-3967-4215)
Institutions
- Université Libre de Bruxelles (BE)
- University of Lisbon (PT)
- Medical University of South Carolina (US)
- Universidade do Porto (PT)
- Hospital de São João (PT)
- Unidade Local de Saúde de Entre Douro e Vouga (PT)
- Hospital Prof. Dr. Fernando Fonseca (PT)
- Nova Medical (United States) (US)
- Hospital de Santo António (PT)
- Hospital da Luz (PT)
- Hospital Beatriz Ângelo (PT)
- Centre for Health Technology and Services Research (PT)
- Walloon Excellence in Lifesciences and Biotechnology (BE)
- i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto (PT)
- University of Aveiro (PT)
- Universidade Nova de Lisboa (PT)
Publication Details
- Journal
- Science Immunology
- Published
- 2026-10-16
- DOI
- https://doi.org/10.1126/sciimmunol.aec9553
- Primary Topic
- Glycosylation and Glycoproteins Research
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Lupus Research Alliance
- Université Libre de Bruxelles
- European Society for Clinical Investigation
- European Federation of Immunological Societies
- Fundação para a Ciência e a Tecnologia
- National Institute of Diabetes and Digestive and Kidney Diseases
- H2020 European Research Council