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

Maeda Y, Rabenow M, Xiang W, Schmid E, Amend L, Otterbein N, Sarfati I, Miyagawa I, Gimaev I, Ehnes L, Lesker TR, Danzer H, Sarter-Zaiss K, Dürholz K, Schälter F, Bao L, Wirtz S, Arnold P, Hofmann J, Sjöberg D, Svärd A, Kastbom A, Schett G, Strowig T, Zaiss M (2025)

Publication Status: Submitted

Publication Type: Unpublished / Preprint

Future Publication Type: Journal article

Publication year: 2025

Publisher: bioRxiv

DOI: 10.1101/2025.03.18.643707

Abstract

An altered gut microbiota, particularly the expansion of Prevotellaceae members, is increasingly implicated in the pathogenesis of rheumatoid arthritis (RA), yet the mechanisms hind this phenomenon remain unclear. Here, we demonstrate that Palleniella intestinalis, a member of the Prevotellaceae family, induces a 100% 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 Th17 differentiation and driving joint inflammation. In vitro, outer membrane vesicles (OMV) from P. intestinalis and Segatella copri (formerly known as Prevotella copri) prime bone marrow-derived dendritic cells (BMDCs) to drive Th17 differentiation in an IL-6-dependent manner. Similar changes with increase in innate immune cell activation and IL-6 levels were shown in gut biopsies from new-onset RA patients. The transfer of Prevotellaceae-derived OMVs or Prevotellaeae-primed BMDCs replicates the hightened 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 Lehrstuhl für Biochemie und Molekulare Medizin Eva Schmid Department of Medicine 3 – Rheumatology and Immunology Nadine Otterbein Professur für Genetik Ilann Sarfati Department of Medicine 3 – Rheumatology and Immunology Ilia Gimaev Lehrstuhl für Innere Medizin III Leona Ehnes Department of Medicine 3 – Rheumatology and Immunology Heike Danzer Lehrstuhl für Genetik Kerstin Sarter-Zaiss Department of Medicine 3 – Rheumatology and Immunology Kerstin Dürholz Department of Medicine 3 – Rheumatology and Immunology Lili Bao Professur für Molekulare Gastroenterologie Stefan Wirtz Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Philipp Arnold Lehrstuhl für Funktionelle und Klinische Anatomie Jörg Hofmann Lehrstuhl für Biochemie Georg Schett Lehrstuhl für Innere Medizin III Mario Zaiss Department of Medicine 3 – Rheumatology and Immunology

Additional Organisation(s)

Graduiertenkolleg 2740/1 - Microenvironmental, Metabolic and Microbial Signals Regulationg Immune Cell-Pathogen Interactions (ImmunoMicroTope 2)

Involved external institutions

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

How to cite

APA:

Maeda, Y., Rabenow, M., Xiang, W., Schmid, E., Amend, L., Otterbein, N.,... Zaiss, M. (2026). Mucosal innate immune activation as the trigger to <i>Prevotella</i> species-induced arthritis in genetically resistant mice. (Unpublished, Submitted).

MLA:

Maeda, Yuichi, et al. Mucosal innate immune activation as the trigger to <i>Prevotella</i> species-induced arthritis in genetically resistant mice. Unpublished, Submitted. 2026.

BibTeX: Download