Dataset Information

CD226 Attenuates Treg Proliferation via Akt and Erk Signaling in an EAE Model.

ABSTRACT: Cluster of differentiation 226 (CD226) molecules play a crucial role in the activation of effector CD4+ T cells during the immune response process, but a cell-intrinsic function of CD226 in CD4+ T subsets is not clear. In this study, we showed that Cd226 -/- mice were resistant to myelin oligodendrocyte glycoprotein peptide 35-55 (MOG35-55)-induced experimental autoimmune encephalomyelitis (EAE) with highly expressed IL-10+CD4+ T cells and downregulated IL-17A+CD4+ T cells when compared with wild-type (WT) mice. Th17 cell infiltration into the central nervous system (CNS) was largely decreased in the absence of CD226 during EAE. CD226 deficiency facilitated the proliferation of regulatory T cells (Tregs), with increased numbers of Tregs observed in EAE mice, and supported the elevated induced regulatory T cell (iTregs) proliferation in vitro. The Akt and Erk signaling pathways were shown to be involved in Cd226 -/- Treg proliferation and function in vivo and in vitro. These findings collectively indicate that CD226 is a key molecule regulating the Treg-mediated suppression of autoimmune responses by inhibiting Treg proliferation. Thus, the results of this study identify additional mechanisms by which CD226 regulates Treg functions in EAE and supports the potential therapeutic effects of anti-CD226 molecules on autoimmune diseases.

SUBMITTER: Wang N

PROVIDER: S-EPMC7478170 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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CD226 Attenuates Treg Proliferation via Akt and Erk Signaling in an EAE Model.

Wang Ning N Yi Hongyu H Fang Liang L Jin Jingyi J Ma Qianli Q Shen Yuting Y Li Juan J Liang Shuang S Xiong Jie J Li Zhuo Z Zeng Hanyu H Jiang Fengliang F Jin Boquan B Chen Lihua L

Frontiers in immunology 20200821

Cluster of differentiation 226 (CD226) molecules play a crucial role in the activation of effector CD4+ T cells during the immune response process, but a cell-intrinsic function of CD226 in CD4+ T subsets is not clear. In this study, we showed that Cd226-/- mice were resistant to myelin oligodendrocyte glycoprotein peptide 35-55 (MOG35-55)-induced experimental autoimmune encephalomyelitis (EAE) with highly expressed IL-10+CD4+</s ...[more]

PMID: 32983109

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Project description:The mammary gland of mammals possesses the specific function of synthesizing, secreting, and delivering milk. Notably, mammary epithelial cells are considered to be central to control the expansion and remodeling of mammary gland into a milk-secretory organ. And the biological function of mammary gland is mainly regulated by the endocrine system, especially for estrogen. G protein-coupled receptor 30 (GPR30), an estrogen membrane receptor, mediates estrogen-induced functions of physiology and pathophysiology. However, the relationship between estrogen/GPR30 signaling and proliferation of goat mammary epithelial cells (gMECs) is still unclear. Herein, estrogen promoted cell proliferation than control, as evidence by upregulation of cell numbers, BrdU-positive cell counts, and cell viability. Of note, these activities were all obviously reduced by treatment with GPR30 antagonist G15, yet GPR30 agonist G1 increased cell proliferation than control. Further, GPR30 silencing inhibited cell proliferation than negative control. This inhibition was accompanied by a G2/M phase arrest and downregulation of cell cycle regulators. Meanwhile, estrogen increased the phosphorylation of ERK1/2 and AKT. Further, the protein level of p-ERK1/2 and p-AKT was enhanced by GPR30 agonist G1 but inhibited by GPR30 antagonist G15 and GPR30 silencing. Importantly, MEK inhibitor and PI3K inhibitor decreased the expression of cell cycle regulators, and repressed estrogen-induced and G1-driven promotion of cell proliferation, suggesting that estrogen regulated cell proliferation of gMECs through mechanisms involving cell cycle, dependent of GPR30 and MEK/ERK and PI3K/AKT signaling pathway. This may provide a strong theoretical basis for researching estrogen sustained-release drugs promoting breast development and improving lactation performance.Abbreviations: gMECs, goat mammary epithelial cells; E2, 17β-estradiol; GPR30, G protein-coupled receptor 30; shRNA, small hairpin RNA; CDK, cyclin-dependent kinase; PI3K, phosphatidylinositol 3-kinase; AKT, proteinkinase B; MAPK, mitogen-activated protein kinase; MEK, mitogen-activated protein kinase kinase; ERK1/2, extracellular signal-regulated kinase 1/2.

Dataset Information

CD226 Attenuates Treg Proliferation via Akt and Erk Signaling in an EAE Model.

Publications

CD226 Attenuates Treg Proliferation via Akt and Erk Signaling in an EAE Model.

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