Analysis of the number and functional activity of T cells in AAA in mice lacking the IL-27 receptor
AbstractIntroduction. Abdominal aortic aneurysm (AАA) is a vascular disease of the abdominal aorta wall caused by the accumulation of large amounts of immune cells, inflammation and destruction of the vessel wall. The progressive growth of an aneurysm frequently leads to its rupture that can be fatal. Knowledge about the potential immune mechanism driving AAA development is still limited, impacting strategy for AAA treatment.
Aim of the study – to determine the role of the interleukin(IL)-27 receptor in the regulation of the number and functional activity of T cells in AАA in mice.
Material and methods. Apoe-/-Il27ra+/- and Apoe-/-Il27ra-/- mice were fed with high-carbohydrate/high fat diet (Western Diet, WD) and implanted with osmotic pumps filled with angiotensin II (Ang II) to induce the development of AAA. The number of T cells and their subpopulations in the suprarenal part of abdominal aorta/AAA tissue was investigated using flow cytometry and immunofluorescence analyses. The production of secreted cytokines was measured by ELISA in the supernatant of cells isolated from the suprarenal part of abdominal aorta/AAA. Two-tailed Student’s t-test was used to compare the 2 mouse groups (Apoe-/-Il27ra+/- and Apoe-/-Il27ra-/-).
Results. Suprarenal part of abdominal aorta/AAA of IL-27R deficient mice were characterized by limited number of T cells, in particular CD4+ and CD8+ subsets, along with reduced production of T-helper (Th) cytokines such as tumor necrosis factor(TNF)α and interferon-γ (IFN-γ) (Th1 cells), IL-4 and IL-13 (Th2 cells), IL-17A (Th17 cells).
Conclusion. Our data demonstrate that IL-27 receptor-mediated signaling affects the number and activation of T cells, suggesting that inhibition of this cytokine signaling pathway can be used to develop immunotherapy for the treatment of AAA.
Keywords:abdominal aortic aneurysm; IL-27 receptor; T cells; cytokines; inflammation
Conflict of interests. The authors declare no conflict of interests.
For citation: Peshkova I.О., Khoreva M.V., Gankovskaya L.V., Koltsova E.K. Analysis of the number and functional activity of T cells in AAA in mice lacking the IL-27 receptor. Immunologiya. 2022; 43 (1): 44–53. DOI: https://doi.org/10.33029/0206-4952-2022-43-1-44-53 (in Russian)
Authors’ contribution. Concept and design of the study – Peshkova I.O., Koltsova E.K.; collection and processing of material – Peshkova I.O.; statistical processing – Peshkova I.O.; text writing – Peshkova I.O., Koltsova E.K., Khoreva M.V.; editing – Peshkova I.O., Koltsova E.K., Khoreva M.V., Gankovskaya L.V.
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