Poster Session 2.C - Molecular Medicine
Kovács-Kemecsei, Éva
CHFPOY
Department of Physiology, Semmelweis University, Budapest, Hungary
06301808944
kemecsei.eva@semmelweis.hu
Lymphatic Ablation Drives Severe Autoimmune Arthritis via Immune Complex-Mediated Inflammation
Éva Kovács-Kemecsei1, Gábor Kovács1, Stella Márta Sági1, Kornél Molnár1, Petra Aradi1, Mohsen Pourmohammad1, Dániel Csete1, Attila Mócsai1, Raghu P. Kataru2, Babak J. Mehrara2, Zoltán Jakus1
1: Department of Physiology, Semmelweis University, Budapest, Hungary
2: Department of Surgery, Division of Plastic and Reconstructive Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
Poszter
Poster Session 2.C - Molecular Medicine
English
Molecular Medicine
Introduction: Rheumatoid arthritis is a chronic autoimmune disorder, primarily affecting the small joints. Despite the known connection between the immune and lymphatic systems, the role of lymphatics in autoimmune arthritis remains unclear.
Aims: Our aim was to investigate the mechanisms by which lymphatic vessels influence the effector phase of autoimmune arthritis.
Methods: Diphtheria toxin-mediated ablation of the local lymphatic vasculature was induced in the hindlimbs of a transgenic mouse model, followed by the induction of arthritis via K/BxN serum transfer. Disease progression was monitored by ankle thickness measurement and clinical scoring. Hindlimb samples were processed for histology, and peripheral autoantibody and local immune-complex levels were measured by ELISA. Local immune cell populations were quantified by flow cytometry, and arthritis-associated bone alterations were assessed by micro-CT.
Results: Lymphatic-deficient mice developed arthritis earlier and displayed more severe progression compared with controls. Histological and micro-CT analysis revealed significantly exacerbated bone erosion and structural damage in lymphatic-deficient arthritic mice. Peripheral autoantibody levels showed no significant differences between arthritic groups. In contrast, local immune-complex accumulation was markedly elevated in lymphatic-deficient arthritic mice, accompanied by a substantial increase in neutrophil infiltration.
Conclusion: Our findings indicate that the local lymphatic vasculature plays a critical immunomodulatory role in the effector phase of autoimmune arthritis. Loss of lymphatic vessels exacerbated autoimmune arthritis, possibly driven by impaired clearance. These results suggest that therapeutic strategies aimed at preserving or enhancing lymphatic function may hold promise in the treatment of autoimmune arthritis.
Funding: National Research, Development and Innovation Office (K139165, TKP2021-EGA-29, TKP2021-EGA-24, 2023-1.2.4-TÉT-2023-00053, 2025-1.2.1-HU-RIZONT-2025-00028), the European Union and the Hungarian Government (VEKOP-2.3.2-16-2016-00002, VEKOP-2.3.3-15-2016-00006), Semmelweis University (STIA-MEC22), Predoctoral Research Fund of the Semmelweis University, Z.J. was a recipient of the János Bolyai Research Scholarship of the Hungarian Academy of Sciences (BO/00898/22)
Semmelweis University
-
Dr. Zoltán Jakus
I do not give consent to the publication of my abstract on the website of the congress.
after finishing doctoral studies with absolutorium (PhD)
Szabad
elfogadva
poszter
nem rendelkezett róla
6128
18:30
18:33