The miR-29a/c-3p/HMCCR pathway is a potential mechanism by which chicken bursa of Fabricius responds to stress affecting immune response.

The bursa of Fabricius (BF), a central immune organ of birds, plays a critical role in immune regulation. Cholesterol metabolism is an important pathway for regulating lymphocyte proliferation and activation. However, the mechanisms by which cholesterol metabolism influences immune regulation in avian BF remain unclear. In this study, dexamethasone (Dex) and Newcastle disease virus (NDV) attenuated vaccine were used to simulate stress and induce immune response in chickens, respectively. The dynamic expression patterns and interrelationships of B cell receptor signaling subunit β (CD79B), sphingosine 1-phosphate receptor 1 (S1PR1), and 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) genes in chicken BF were analyzed, and the miRNA regulatory mechanisms of cholesterol metabolism were further identified. The results showed that, under stress condition, the BF actively responded to stress processes by circulating B cells migrating into BF, and exhibited similar changes in the primary and secondary stresses; under immune response condition, the BF participated in immune responses primarily through the migration of B cells from BF into circulatory system, which showed differences between the primary and secondary immune response. BF responded to stress mainly through up-regulating cholesterol metabolism, and the change in cholesterol metabolism was one of potential key pathways by which stress inhibited the immune function of BF. Moreover, the dynamic migrations of B cells and changes of cholesterol metabolism in BF possibly constituted the two-way regulatory modes to maintain the immune homeostasis of BF. The miR-29a/c-3p/HMGCR pathway served as a potential mechanism for cholesterol metabolism in chicken BF under different immune conditions. This study can provide innovative references for further exploring the mechanisms of stress affecting the immune function of BF.