Research Article: CCL25 chemokine promotes antiviral tissue resident CD4 + and CD8 + effector memory T RM cells associated with a reduction of ocular herpes infection and disease: a potential gut–eye axis in herpes immunity
Abstract:
CCL25, a mucosal chemokine mainly produced in the gut, is known for its role in intestinal immunity through CCR9. In this study, we tested whether CCL25 also contributes to ocular immunity within the gut-eye axis during herpes simplex virus type 1 (HSV-1) infection. Using CCL25-deficient (CCL25 (–/–) deficient) mice and wild-type C57BL/6J controls, which were infected ocularly with HSV-1 (McKrae strain), we found that CCL25 deficiency led to more severe corneal disease, increased viral replication, and reduced survival. CCL25 (–/–) deficient mice also had fewer antiviral effector memory CD44 + CD4 + and CD44 + CD8 + T cells in the cornea, gastrointestinal tract, and draining lymph nodes, as well as reduced numbers of activated tissue-resident CD69 + CD103 + CD4 + and CD69 + CD103 + CD8 + T RM cells that produced interferon-?. Immunohistochemistry showed strong CCL25 expression in the gut of wild-type mice but not in the cornea or conjunctiva. In addition, the mucosal chemokines CXCL14, CXCL17, and CCL28 were upregulated in infected ocular tissues of wild-type mice but remained low in CCL25 (–/–) deficient mice, suggesting that CCL25 influences the expression of major mucosal chemokines. Collectively, these findings indicate that CCL25 supports recruitment of antiviral corneal tissue-resident effector memory T RM cells during ocular HSV-1 infection and supports the concept of a gut-eye axis in herpes immunity. The CCL25/CCR9 pathway may represent a promising therapeutic target to protect from herpetic eye disease.
Introduction:
Herpes simplex virus type 1 (HSV-1) is the leading cause of infectious corneal blindness in the developed world, with an estimated 1.5 million cases of HSV keratitis annually and approximately 40,000 new cases of severe visual impairment or blindness each year ( 1 ). The most vision-threatening manifestation is recurrent herpetic stromal keratitis (HSK), a chronic immunoinflammatory condition driven by repeated HSV-1 reactivation in the corneal stroma, leading to progressive immunopathology, corneal scarring,…
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