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Peer-reviewedCC BY 4.0Frontiers in Immunology

Tolerogenic dendritic cells attenuate collagen-induced arthritis through a mucosal immunity–gut microbiota–butyrate axis

  • Xiufang Wan1,2
  • Yan Zhou2
  • Tiaoyu Long3
  • Rui Yuan1,2
  • Lunmin Bao4
  • Honghong Li5
  • Ping Shi2
  • Rui Gong2
  • Shirong Yan2
  • Qingqing Wu2
  • Hongmei Jiang1,6
6 affiliations
  1. 1School of Clinical Laboratory Science, Guizhou Medical University
  2. 2Center for Clinical Laboratories, The Affiliated Hospital of Guizhou Medical University
  3. 3Department of Laboratory Medicine, The Second Affiliated Hospital of Guizhou University of Traditional Chinese Medicine
  4. 4Department of Laboratory Medicine, Anshun City People’s Hospital
  5. 5Department of Tuberculosis, Affiliated Hospital of Zunyi Medical University
  6. 6Department of Medical Technology, Zunyi Medical and Pharmaceutical College
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Abstract

Background: Tolerogenic dendritic cells (TolDCs) are being developed to restore antigen-specific immune tolerance in autoimmune diseases. However, whether their therapeutic effects in autoimmune arthritis involve modulation of the gut–joint axis remains unclear.

Methods: TolDCs generated using an NF-κB decoy oligodeoxynucleotide were loaded with bovine type II collagen and administered to rats with collagen-induced arthritis (CIA). Arthritis severity was assessed clinically and histologically. Antibiotic-mediated microbiota depletion and fecal microbiota transplantation (FMT) were used to assess microbiota involvement. Colonic tight-junction protein expression, mesenteric lymph node Treg/Th17 balance, fecal microbial communities, PICRUSt2-predicted short-chain fatty acid (SCFA)-related metabolic functions based on 16S rRNA sequencing data, serum SCFAs, and the effects of sodium butyrate supplementation were also evaluated.

Results: TolDCs reduced paw swelling and arthritis scores and ameliorated ankle-joint pathology. In the concurrent antibiotic-depletion experiment, TolDC-associated improvements in arthritis outcomes did not reach statistical significance, whereas FMT from TolDC-treated donors partially transferred protection to antibiotic-pretreated CIA recipients. TolDC treatment increased colonic ZO-1 and occludin expression, shifted the mesenteric lymph node Treg/Th17 balance toward a regulatory profile, altered gut microbial community structure and composition, and was accompanied by higher predicted abundances of selected butyrate-associated MetaCyc pathways and KEGG Orthology (KO) functional groups, along with increased serum butyrate concentrations. Sodium butyrate supplementation partially reproduced the protective phenotype.

Conclusion: These findings support a microbiota-dependent component of TolDC-mediated protection and suggest that a coordinated mucosal immunity–gut microbiota–butyrate axis may contribute to arthritis control.

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Cite

BibTeXRIS
BibTeX
@article{wan2026tolerogenic,
  title = {{Tolerogenic dendritic cells attenuate collagen-induced arthritis through a mucosal immunity–gut microbiota–butyrate axis}},
  author = {Xiufang Wan and Yan Zhou and Tiaoyu Long and Rui Yuan and Lunmin Bao and Honghong Li and Ping Shi and Rui Gong and Shirong Yan and Qingqing Wu and Hongmei Jiang},
  journal = {Frontiers in Immunology},
  year = {2026},
  month = oct,
  doi = {10.3389/fimmu.2026.1971542},
  url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1971542/full},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Tolerogenic dendritic cells attenuate collagen-induced arthritis through a mucosal immunity–gut microbiota–butyrate axis
AU  - Xiufang Wan
AU  - Yan Zhou
AU  - Tiaoyu Long
AU  - Rui Yuan
AU  - Lunmin Bao
AU  - Honghong Li
AU  - Ping Shi
AU  - Rui Gong
AU  - Shirong Yan
AU  - Qingqing Wu
AU  - Hongmei Jiang
PY  - 2026
DA  - 2026/10/29
JO  - Frontiers in Immunology
DO  - 10.3389/fimmu.2026.1971542
UR  - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1971542/full
AB  - Background: Tolerogenic dendritic cells (TolDCs) are being developed to restore antigen-specific immune tolerance in autoimmune diseases. However, whether their therapeutic effects in autoimmune arthritis involve modulation of the gut–joint axis remains unclear.  Methods: TolDCs generated using an NF-κB decoy oligodeoxynucleotide were loaded with bovine type II collagen and administered to rats with collagen-induced arthritis (CIA). Arthritis severity was assessed clinically and histologically. Antibiotic-mediated microbiota depletion and fecal microbiota transplantation (FMT) were used to assess microbiota involvement. Colonic tight-junction protein expression, mesenteric lymph node Treg/Th17 balance, fecal microbial communities, PICRUSt2-predicted short-chain fatty acid (SCFA)-related metabolic functions based on 16S rRNA sequencing data, serum SCFAs, and the effects of sodium butyrate supplementation were also evaluated.  Results: TolDCs reduced paw swelling and arthritis scores and ameliorated ankle-joint pathology. In the concurrent antibiotic-depletion experiment, TolDC-associated improvements in arthritis outcomes did not reach statistical significance, whereas FMT from TolDC-treated donors partially transferred protection to antibiotic-pretreated CIA recipients. TolDC treatment increased colonic ZO-1 and occludin expression, shifted the mesenteric lymph node Treg/Th17 balance toward a regulatory profile, altered gut microbial community structure and composition, and was accompanied by higher predicted abundances of selected butyrate-associated MetaCyc pathways and KEGG Orthology (KO) functional groups, along with increased serum butyrate concentrations. Sodium butyrate supplementation partially reproduced the protective phenotype.  Conclusion: These findings support a microbiota-dependent component of TolDC-mediated protection and suggest that a coordinated mucosal immunity–gut microbiota–butyrate axis may contribute to arthritis control.
SN  - 1664-3224
ER  -