Molecular Medicine II.
Ms. Kemecsei, Éva
CHFPOY
Semmelweis University, Department of Physiology
06301808944
kemecsei.eva@semmelweis.hu
Characterization of the Role of Lymphatics in Autoimmune Arthritis
Eva Kemecsei1, Gábor Kovács1, Stella Sági1, Kornél Molnár1, Petra Aradi1, 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
Szóbeli
Molecular Medicine II.
English
Molecular Medicine
Introduction: Rheumatoid arthritis is a chronic autoimmune disease, characterized by an inflammatory polyarthritis primarily affecting the small joints. The disease often results in progressive joint destruction and disability. The relationship between the immune system and lymphatic system has been known, but the involvement of lymphatics in the development of autoimmune inflammatory diseases remains unclear.
Aims: Our aim was to characterize the role of the lymphatics in the effector phase of autoimmune arthritis in mouse models.
Methods: In our studies Flt4Cre-ERT2; iDTRfl/fl transgenic mouse model was used to induce local deletion of lymphatic vessels in the hind limb by diphtheria toxin injection. Using the K/BxN serum transfer arthritis model, arthritic or control serum was injected into previously diphtheria toxin-treated animals and mice with intact lymphatics. The disease progression was monitored by the assessment of ankle thickness and clinical score. Hind limb samples were processed for paraffin-based histology. Peripheral autoantibody levels and local immune complex levels were measured by ELISA. Immune cell populations of the ankle tissue were quantified by flow cytometry. Bone structure alteration was characterized in arthritic mice via micro-CT.
Results: In lymphatic deficient mice, arthritis developed in an earlier phase and more severe disease progression was observed compared to arthritic mice with intact lymphatics. Autoantibody levels in peripheral blood peaked one day after serum transfer and was followed by a decreasing tendency. Local immunocomplex levels were significantly higher in lymphatic deficient arthritic mice compared to arthritic mice with intact lymphatics. Flow cytometry results showed a significant increase in neutrophil granulocyte count in lymphatic deficient mice. More prominent bone destruction was detected in lymphatic deficient arthritic mice compared to mice with intact lymphatics.
Conclusion: The lack of lymphatics in the affected areas resulted in more severe disease progression, which suggests that lymphatics participate in immunomodulation in autoimmune arthritis. These findings can contribute to gain more knowledge on the pathomechanism of autoimmune arthritic processes.
Funding: K139165, TKP2021-EGA-29, TKP2021-EGA-24, Scientific and Innovative Research Fund of Semmelweis Univ.
Semmelweis University
Zoltán Jakus MD PhD
I do not give consent to the publication of my abstract on the website of the congress.
Szabad
elfogadva
szóbeli
nem rendelkezett róla
6128
17:00
17:10