Molecular Sciences IV.
Kemecsei, Éva, MSc
CHFPOY
Semmelweis University, Department of Physiology
06301808944
kemecsei.eva@med.semmelweis-univ.hu
Characterization of the Role of Lymphatics in Autoimmune Arthritis
Éva Kemecsei1, Gábor Kovács1, Petra Aradi1, Stella Sági1, Kornél Molnár1, Raghu P. Kataru2, Babak J. Mehrara2 and 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 Sciences IV.
English
Molecular Sciences
Introduction: Rheumatoid arthritis is a chronic autoimmune disease, characterized by 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 lymphatics in the development of autoimmune arthritis in a transgenic mouse model.
Method: In our studies we used the Flt4Cre-ERT2; iDTRfl/fl transgenic model to induce local deletion of lymphatic vessels in the hind limb by diphtheria toxin injection. K/BxN serum transfer arthritis model was used for disease induction. Arthritis progression was monitored by the assessment of ankle thickness and clinical score. Hind limb samples were processed for paraffin-based histology. Peripheral autoantibody titers and local immunocomplex levels were determined. Immune cell populations of the ankle tissue were quantified by flow cytometry.
Results: We effectively induced the local deletion of lymphatics in the hind limb. In lymphatic deficient mice, the disease progression was more severe compared to arthritic mice with intact lymphatics. Arthritis induction resulted in dynamically changing lymphatic morphology in the joint area. Peripheral autoantibody titers 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 compared to mice with intact lymphatics.
Conclusion: Our results suggest that lymphatics are involved in the pathogenesis of autoimmune arthritis. In our ongoing experiments, we are determining the cytokine production of arthritic ankles and characterizing the bone destruction in ankle samples. These findings might help to gain more knowledge on the pathomechanism of autoimmune arthritic processes.
Funding: K139165, TKP2021-EGA-29, TKP2021-EGA-24, VEKOP-2.3.2-16-2016-00002, Scientific and Innovative Research Fund of Semmelweis Univ. and Higher Education Institutional Excellence Program of the Ministry for Innovation and Technology
Semmelweis University, Doctoral School of Molecular Medicine
Dr Zoltán Jakus
I do not give consent to the publication of my abstract on the website of the congress.
Szabad
elfogadva
szóbeli
nem rendelkezett róla
6128
15:15
15:30
Éva Kemecsei1, Gábor Kovács1, Petra Aradi1, Stella Sági1, Kornél Molnár1, Raghu P. Kataru2, Babak J. Mehrara2 and 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