PEDV regulates trans-mammary epithelial migration of T cells in a CCR10/CCL28-dependent manner

PEDV以CCR10/CCL28依赖的方式调节T细胞的跨乳腺上皮迁移。

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Abstract

Porcine epidemic diarrhea virus (PEDV) is a re-emerging coronavirus that infects neonatal piglets via newly discovered colostrum transmission routes. Research has shown that T cells carrying PEDV in colostrum can infect piglets, but the mechanism is unclear. This study revealed that PEDV impairs T-cell immune function, preventing the production of granzymes, perforin, and interferon-γ. Furthermore, RNA sequencing of PEDV-infected and uninfected T cells revealed significant differences in gene expression: the expression of CCR10 on T-cell surfaces increased, whereas the expression of vinculin, α-actinin, paxillin, FAK, and talin-1 decreased (P < 0.05). The results revealed that CCR10 only interacts with CCL28. PEDV strains led to significant upregulation of CCL28 in porcine mammary epithelial cells (PMECs). Finally, the role of CCR10/CCL28 in T-cell migration during PEDV infection was illustrated via a small interfering RNA (siRNA)-mediated knockdown method and a coculture model of PMECs with T cells. The results demonstrated that the addition of the chemokine CCL28 to the lower chamber of the transwell system elicits a chemotactic effect on T cells. This phenomenon is attributed mainly to the substantial increase in the expression levels of paxillin and FAK on the surface of T cells following siRNA-mediated interference with CCR10. In contrast, no significant differences were observed in the expression levels of vinculin and α-actinin. These results suggest a mechanism underlying the regulation of T-cell migration in response to CCL28, which is potentially associated with the modulation of paxillin and FAK expression levels. IMPORTANCE: Understanding the impact of porcine epidemic diarrhea virus (PEDV) on T-cell function and migration is crucial. This study reveals PEDV impairs T-cell immunity by preventing key molecule production. It uncovers significant gene expression changes in infected T cells, with CCR10 rising and several adhesion-related proteins falling. Further, CCR10 interacts solely with CCL28, and PEDV upregulates CCL28 in PMECs, is key. The transwell system experiments show CCL28's chemotactic effect on T cells, linked to paxillin and FAK expression changes. These findings shed light on how PEDV manipulates T-cell migration via the CCR10/CCL28 axis, aiding in developing strategies against PEDV.

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