Notch Signaling Pathway Promotes Th17 Cell Differentiation and Participates in Thyroid Autoimmune Injury in...

Area of Science:

• Immunology
• Endocrinology
• Molecular Biology

Background:

• Experimental autoimmune thyroiditis (EAT) is an autoimmune disorder affecting the thyroid gland.
• T helper 17 (Th17) cells play a crucial role in the pathogenesis of various autoimmune diseases.
• The Notch signaling pathway is implicated in immune cell differentiation and function.

Purpose of the Study:

• To investigate the role of the Notch signaling pathway in the development of EAT.
• To determine if Notch signaling influences Th17 cell differentiation and function in EAT.
• To explore the therapeutic potential of targeting Notch signaling in EAT.

Main Methods:

• EAT was induced in mice using porcine thyroid immunoglobulin (pTg).
• Mice were treated with DAPT, a Notch signaling inhibitor.
• Thyroiditis severity, Th17 cell percentages, and expression of RORγt, IL-17A, and Notch pathway components were assessed using histology, flow cytometry, RT-qPCR, and ELISA.

Main Results:

• Notch pathway components were upregulated in EAT mice.
• DAPT treatment significantly reduced thyroiditis, Th17 cell proportions, and IL-17A levels in vivo and in vitro.
• Th17 cell percentages positively correlated with disease severity and IL-17A concentrations.

Conclusions:

• The Notch signaling pathway is involved in the pathogenesis of EAT.
• Inhibition of Notch signaling alleviates thyroiditis by suppressing Th17 cell differentiation and function.
• Targeting the Notch pathway represents a potential therapeutic strategy for autoimmune thyroid diseases.