The effects of endometrial epithelium-derived exosomes on the recruitment and activation of T Lymphocytes in the uteri of dairy cows

Abstract

Endometritis is caused by endometrial cell injury and chronic inflammation of uteri infected by pathogens, leading to reproductive failure in dairy cows. Changes of the endometrial immune response regulates the development of endometritis. In a recent discovery, exosomes acted as a functional regulator secreted by a variety of cells, however, its regulatory mechanism in the local immune response of the uteri is still unclear. In this study, flow cytometry was performed to identify the increased number of T lymphocytes, namely Tc cells, in the uteri with endometritis while the Th and Treg cells decreased very significantly. Moreover, the functional marker factors FOXP3 of Treg cells and Th17 cells were significantly decreased and increased, respectively. The mRNA expression of immune tolerance regulators PD1, CTLA4 and Galectin-1 in the group of Treg cells which were co-incubated with LPS-stimulated endometrial epithelium-derived exosomes was recorded to be significantly lower than the Treg cells which were co-incubated with normal EEC-derived exosomes. Furthermore, the protein expression of PD1, CTLA4, Galectin-1, Foxp3 and IL-17 was consistent with the results in the Treg cells co-incubated with different source exosomes in CTLL-2 cells. It was demonstrated that endometrial epithelium-derived exosomes act as a vital regulator of changes in the composition and function of T lymphocyte subsets in the uteri of dairy cows.