Tissue-Resident and Effector-Memory Lymphocyte Recruitment to the Ocular Mucosa Requires CCL28/CCR10 Signaling During Recurrent HSV-1 Infection
- 1University of California Irvine
Abstract
Ocular herpes simplex virus type 1 (HSV-1) infection is a major cause of infectious corneal disease that can lead to recurrent herpetic keratitis, chronic inflammation, and vision loss. Although effective antiviral immunity is essential for controlling HSV-1 and limiting recurrent disease, the mechanisms regulating recruitment of protective lymphocytes to the ocular mucosa remain incompletely understood. CCL28 is a mucosa-associated chemokine expressed at epithelial surfaces that signals through its receptor CCR10, expressed by distinct antiviral T- and B-cell subsets. Using a mouse model of recurrent ocular HSV-1 infection, we investigated the role of the CCL28/CCR10 axis in mobilizing protective HSV-1-specific immune cells to the ocular mucosa (OM). Following infection, wild-type (WT) B6 mice showed a marked increase in CCL28 expression within the OM, coinciding with accumulation of HSV-specific effector-memory (CCR10+CD44+CD62L-) T cells and CCR10+B220+ B cells in the OM and trigeminal ganglia (TG). These cells displayed an antigen-experienced, effector-memory phenotype, suggesting that CCL28/CCR10 signaling contributes to a localized antiviral immune response in the ocular mucosa. By contrast, CCL28-deficient (CCL28(-/-)) mice: (i) were more susceptible to recurrent ocular HSV-1 infection; (ii) exhibited significantly reduced frequencies of HSV-specific effector-memory (CCR10+CD44+CD62L-) and tissue-resident memory (CCR10+CD69+CD103+) T cells, as well as CCR10+B220+ B cells, in the infected OM and TG; and (iii) showed diminished effector function (IFN-{gamma}, TNF, and Granzyme B production) in these populations, associated with increased viral burden and ocular pathology. These findings identify the CCL28/CCR10 axis as a critical regulator of antiviral B- and T-cell trafficking to the ocular mucosa, contributing to protection against recurrent herpetic eye disease and providing a mechanistic basis for targeting mucosal chemokine pathways to improve vaccine strategies against ocular herpes.
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BibTeX
@misc{karan2026tissueresident,
title = {{Tissue-Resident and Effector-Memory Lymphocyte Recruitment to the Ocular Mucosa Requires CCL28/CCR10 Signaling During Recurrent HSV-1 Infection}},
author = {S. Karan and S. Prakash and M. Chhaya and S. X. LeNg and L. BenMohamed},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.14.751393},
url = {https://www.biorxiv.org/content/10.64898/2026.09.14.751393v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Tissue-Resident and Effector-Memory Lymphocyte Recruitment to the Ocular Mucosa Requires CCL28/CCR10 Signaling During Recurrent HSV-1 Infection
AU - S. Karan
AU - S. Prakash
AU - M. Chhaya
AU - S. X. LeNg
AU - L. BenMohamed
PY - 2026
DA - 2026/09/14
PB - bioRxiv
DO - 10.64898/2026.09.14.751393
UR - https://www.biorxiv.org/content/10.64898/2026.09.14.751393v1
AB - Ocular herpes simplex virus type 1 (HSV-1) infection is a major cause of infectious corneal disease that can lead to recurrent herpetic keratitis, chronic inflammation, and vision loss. Although effective antiviral immunity is essential for controlling HSV-1 and limiting recurrent disease, the mechanisms regulating recruitment of protective lymphocytes to the ocular mucosa remain incompletely understood. CCL28 is a mucosa-associated chemokine expressed at epithelial surfaces that signals through its receptor CCR10, expressed by distinct antiviral T- and B-cell subsets. Using a mouse model of recurrent ocular HSV-1 infection, we investigated the role of the CCL28/CCR10 axis in mobilizing protective HSV-1-specific immune cells to the ocular mucosa (OM). Following infection, wild-type (WT) B6 mice showed a marked increase in CCL28 expression within the OM, coinciding with accumulation of HSV-specific effector-memory (CCR10+CD44+CD62L-) T cells and CCR10+B220+ B cells in the OM and trigeminal ganglia (TG). These cells displayed an antigen-experienced, effector-memory phenotype, suggesting that CCL28/CCR10 signaling contributes to a localized antiviral immune response in the ocular mucosa. By contrast, CCL28-deficient (CCL28(-/-)) mice: (i) were more susceptible to recurrent ocular HSV-1 infection; (ii) exhibited significantly reduced frequencies of HSV-specific effector-memory (CCR10+CD44+CD62L-) and tissue-resident memory (CCR10+CD69+CD103+) T cells, as well as CCR10+B220+ B cells, in the infected OM and TG; and (iii) showed diminished effector function (IFN-{gamma}, TNF, and Granzyme B production) in these populations, associated with increased viral burden and ocular pathology. These findings identify the CCL28/CCR10 axis as a critical regulator of antiviral B- and T-cell trafficking to the ocular mucosa, contributing to protection against recurrent herpetic eye disease and providing a mechanistic basis for targeting mucosal chemokine pathways to improve vaccine strategies against ocular herpes.
ER -