Molecular Sciences IV.
Kemecsei, Éva, MSc
Department of Physiology
+36301808944
kemecsei.eva@med.semmelweis-univ.hu
Effect of Inducible Deletion of Lymphatic Vessels in Development of Autoimmune Arthritis
Éva Kemecsei1, Gábor Kovács1, Petra Aradi1, Babak J. Mehrara2; Raghu P. Kataru2 and Zoltán Jakus1
1 Department of Physiology, Semmelweis University, Budapest
2 Department of Surgery, Division of Plastic and Reconstructive Surgery, Memorial Sloan Kettering Cancer Center, New York, NY USA
Szóbeli
Molecular Sciences IV.
Hungarian
Molecular Sciences
Introduction: Rheumatoid arthritis is a chronic autoimmune disease, characterized by an inflammatory polyarthritis affecting primarily small joints. This disease often results in progressive joint destruction and disability. The relationship between the immune and lymphatic systems has been explored, but the possible role of lymphatics in the development of autoimmune inflammatory diseases remains unclear.
Aims: Our aim was to characterize the role of the lymphatics in development of autoimmune arthritis in a mouse model with an inducible deletion of the lymphatic vessels.
Methods: In our studies we used the Flt4Cre-ERT2; iDTRfl/fl transgenic model to induce the diphtheria toxin (DT) mediated deletion of lymphatic vessels in the hind limb. Using the K/BxN serum transfer model, arthritic serum was injected into DT-treated and non-treated animals. Monitoring the disease progression, ankle thickness and clinical score were assigned. Peripheral autoantibody levels were quantified at different time points after serum injection. Immune cell populations of the ankle tissue were quantified by flow cytometry.
Results: We effectively induced the local deletion of lymphatics. In lymphatic deleted mice, arthritis developed in an earlier phase and showed more severe progression compared to arthritic mice with intact lymphatic. Determination of peripheral autoantibody levels show that the autoantibody titers peaked one day after serum transfer and was followed by a decreasing tendency. Flow cytometry results show that in arthritic mice, neutrophil granulocyte count was significantly higher in lymphatic deficient mice compared to mice with intact lymphatics.
Conclusion: Our results suggest that the lymphatic system takes part in the pathogenesis and severity of autoimmune arthritis. In our ongoing experiments, we are working on developing a method to detect the immune complex levels of the ankle joint, moreover, our further goal is to determine which cytokines are dominant in the arthritic ankle. These findings will contribute to gain more knowledge on the patomechanism of rheumatoid arthritis.
Funding: K139165, TKP2021-EGA-29, TKP2021-EGA-24, VEKOP-2.3.2-16-2016-00002 and EFOP-3.6.3-VEKOP-16-2017-00009, Scientific and Innovative Research Fund of Semmelweis University and Higher Education Institutional Excellence Program of the Ministry for Innovation and Technology
Semmelweis University, Doctoral School of Molecular Medicine
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
15:30
15:45
Éva Kemecsei1, Gábor Kovács1, Petra Aradi1, Babak J. Mehrara2; Raghu P. Kataru2 and Zoltán Jakus1
1 Department of Physiology, Semmelweis University, Budapest
2 Department of Surgery, Division of Plastic and Reconstructive Surgery, Memorial Sloan Kettering Cancer Center, New York, NY USA