Mucosal innate immune activation as the trigger to Prevotella species-induced arthritis in genetically resistant mice

Maeda Y, Rabenow M, Xiang W, Schmid E, Otterbein N, Gimaev I, Amend L, Riedinger L, Ehnes L, Miyagawa I, Sarfati I, Lesker TR, Danzer H, Sarter K, Dürholz K, Schälter F, Bao L, Wirtz S, Arnold P, Hofmann J, Pischetsrieder M, Sjöberg D, Svärd A, Kastbom A, Schett G, Strowig T, Zaiss M (2026)

Publication Type: Journal article

Publication year: 2026

Journal

Cell Reports Elsevier (Cell Press)

Book Volume: 45

Pages Range: 116755-

Journal Issue: 1

DOI: 10.1016/j.celrep.2025.116755

Abstract

An altered gut microbiota, particularly the expansion of Prevotellaceae members, is implicated in the pathogenesis of rheumatoid arthritis (RA), yet the mechanisms behind this phenomenon remain unclear. Here, we demonstrate that Palleniella intestinalis, a member of the Prevotellaceae family, induces 100% of arthritis incidence in genetically resistant C57BL/6 mice. Inoculation with P. intestinalis modifies gut microbiota ecology, increases intestinal permeability, and selectively activates colonic CD11b+CD11c+ myeloid cells, facilitating T helper 17 (Th17) differentiation and driving joint inflammation. In vitro, outer membrane vesicles (OMVs) from P. intestinalis and Segatella copri (formerly known as Prevotella copri) prime bone marrow-derived dendritic cells (BMDCs) to drive Th17 differentiation in an interleukin-6 (IL-6)-dependent manner. Similar innate immune activation with elevated IL-6 levels was observed in gut biopsies from new-onset patients with RA. Transfer of Prevotellaceae-derived OMVs or Prevotellaeae-primed BMDCs replicates the heightened arthritis incidence in resistant mice, highlighting the critical role of intestinal immune activation in RA.

Authors with CRIS profile

Yuichi Maeda Department of Medicine 3 – Rheumatology and Immunology Wei Xiang Department of Molecular Neurology Eva Schmid Department of Medicine 3 – Rheumatology and Immunology Nadine Otterbein Department of Medicine 3 – Rheumatology and Immunology Ilia Gimaev Lehrstuhl für Innere Medizin III Lena Riedinger FAU Forschungszentrum Neue Wirkstoffe (FAU NeW) Leona Ehnes Department of Medicine 3 – Rheumatology and Immunology Ilann Sarfati Department of Medicine 3 – Rheumatology and Immunology Kerstin Sarter-Zaiss Department of Medicine 3 – Rheumatology and Immunology Kerstin Dürholz Department of Medicine 3 – Rheumatology and Immunology Lili Bao Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Stefan Wirtz Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Philipp Arnold Lehrstuhl für Funktionelle und Klinische Anatomie Jörg Hofmann Lehrstuhl für Biochemie Monika Pischetsrieder Lehrstuhl für Lebensmittelchemie (Henriette-Schmidt-Burkhardt Lehrstuhl) Georg Schett Lehrstuhl für Innere Medizin III Mario Zaiss Department of Medicine 3 – Rheumatology and Immunology

Involved external institutions

Helmholtz-Zentrum für Infektionsforschung (HZI) DE Germany (DE) Uppsala University SE Sweden (SE) Linköpings universitet / Linköping University SE Sweden (SE)

How to cite

APA:

Maeda, Y., Rabenow, M., Xiang, W., Schmid, E., Otterbein, N., Gimaev, I.,... Zaiss, M. (2026). Mucosal innate immune activation as the trigger to Prevotella species-induced arthritis in genetically resistant mice. Cell Reports, 45(1), 116755-. https://doi.org/10.1016/j.celrep.2025.116755

MLA:

Maeda, Yuichi, et al. "Mucosal innate immune activation as the trigger to Prevotella species-induced arthritis in genetically resistant mice." Cell Reports 45.1 (2026): 116755-.

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