Immunomolecular and reactivity landscapes of gut IgA subclasses in homeostasis and inflammatory bowel disease
The human gut includes plasma cells (PCs) expressing immunoglobulin A1 (IgA1) or IgA2, two structurally distinct IgA subclasses with elusive regulation, function, and reactivity. We show here that intestinal IgA1+ and IgA2+ PCs co-emerged early in life, comparably accumulated somatic mutations, and were enriched within short-lived CD19+ and long-lived CD19- PC subsets, respectively. IgA2+ PCs were extensively clonally related to IgA1+ PCs and a subset of them presumably emerged from IgA1+ precursors. Of note, secretory IgA1 (SIgA1) and SIgA2 dually coated a large fraction of mucus-embedded bacteria, including Akkermansia muciniphila. Disruption of homeostasis by inflammatory bowel disease (IBD) was associated with an increase in actively proliferating IgA1+ plasmablasts, a depletion in long-lived IgA2+ PCs, and increased SIgA1+SIgA2+ gut microbiota. Such increase featured enhanced IgA1 reactivity to pathobionts, including Escherichia coli, combined with depletion of beneficial A. muciniphila. Thus, gut IgA1 and IgA2 emerge from clonally related PCs and show unique changes in both frequency and reactivity in IBD.
Authors
- J.E. Castillo Guerra (ORCID: https://orcid.org/0000-0001-7185-9283)
- Mònica Gonzàlez‐Farré (ORCID: https://orcid.org/0000-0002-0653-0980)
- Daniel Segura-Garzón (ORCID: https://orcid.org/0000-0003-0210-9571)
- Marta Garrido‐Pontnou (ORCID: https://orcid.org/0000-0002-7762-7085)
- Francisco Guarner (ORCID: https://orcid.org/0000-0002-4051-0836)
- Laura Comerma (ORCID: https://orcid.org/0000-0002-0249-4636)
- Xavi Marcos-Fa (ORCID: https://orcid.org/0000-0002-4216-1123)
- Roser Tachó‐Piñot (ORCID: https://orcid.org/0000-0002-4641-1134)
- Mathieu Uzzan (ORCID: https://orcid.org/0000-0002-7761-2879)
- Joan Lop (ORCID: https://orcid.org/0000-0002-9442-5688)
- Andrea Cerutti (ORCID: https://orcid.org/0000-0003-3026-4704)
- Celia Corral-Vázquez (ORCID: https://orcid.org/0000-0002-0621-4590)
- Giuliana Magri (ORCID: https://orcid.org/0000-0002-0163-3542)
- Hadas Neuman
- Lucía Márquez (ORCID: https://orcid.org/0000-0002-3182-9570)
- Ramit Mehr (ORCID: https://orcid.org/0000-0002-4303-6834)
- Saurabh Mehandru (ORCID: https://orcid.org/0000-0001-9781-2969)
- Lisa Perruzza
- Sonia Tejedor Vaquero (ORCID: https://orcid.org/0000-0003-2873-4981)
- Emilie K. Grasset (ORCID: https://orcid.org/0000-0002-9592-1640)
- Fabio Grassi (ORCID: https://orcid.org/0000-0003-3348-1712)
- Júlia Perera‐Bel (ORCID: https://orcid.org/0000-0002-6809-132X)
- Adam Rosenstein
- Mónica Martínez‐Gallo
- Marc Pybus (ORCID: https://orcid.org/0000-0002-6195-5738)
- Encarna Varela (ORCID: https://orcid.org/0000-0001-6334-9320)
- María Evangelina Patriarca-Amiano (ORCID: https://orcid.org/0000-0003-1001-1910)
- Jordi Sintes (ORCID: https://orcid.org/0000-0002-1836-7076)
- Pau Berenguer‐Molins (ORCID: https://orcid.org/0000-0002-0170-2931)
- Pablo Santiago Díaz (ORCID: https://orcid.org/0000-0003-2219-7687)
- Mar Iglesias (ORCID: https://orcid.org/0000-0002-2274-4671)
- Andrea Martín-Nalda (ORCID: https://orcid.org/0000-0002-3590-0186)
- Mónica Larrubia-Loring (ORCID: https://orcid.org/0009-0002-9054-9269)
Institutions
- Institució Catalana de Recerca i Estudis Avançats (ES)
- Universitat Autònoma de Barcelona (ES)
- Bar-Ilan University (IL)
- Vall d'Hebron Institut de Recerca (ES)
- Vall d'Hebron Hospital Universitari (ES)
- Hospital Del Mar (ES)
- Hospital del Mar Research Institute (ES)
- Jeffrey Modell Foundation (AU)
- Medical Research Network (US)
- Università della Svizzera italiana (CH)
- Icahn School of Medicine at Mount Sinai (US)
Publication Details
- Journal
- The Journal of Experimental Medicine
- Published
- 2024-11-19
- DOI
- https://doi.org/10.1084/jem.20230079
- Citations
- 13
- Primary Topic
- Immune Cell Function and Interaction
- Type
- article
- Field-Weighted Citation Impact
- 3.13
Funders
- Crohn's and Colitis Foundation of America
- United States - Israel Binational Science Foundation
- Universitat Pompeu Fabra
- Ministerio de Economía y Competitividad
- Ministerio de Ciencia e Innovación
- National Institutes of Health
- Instituto de Salud Carlos III
- European Regional Development Fund