REVIEW article
Front. Immunol.
Sec. Viral Immunology
This article is part of the Research TopicExploring Herpesviruses: From Biology to Disease Management and PreventionView all 6 articles
Role of Mucosal Chemokines in the Development of Tissue-Resident CD4+ and CD8+ TRM Cells to Fend Off Herpes Simplex Infections
Provisionally accepted
LBACHIR BENMOHAMED*
Yassir Lekbach
Aziz Chentoufi
Swayam Prakash
Sweta KaranKathy K Hormi-Carver
Joshua Dorotta
Afshana Quadiri- University of California, Irvine, Irvine, United States
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The mucosal immune system represents the largest and most significant component of the immune network, providing critical defense against infectious pathogens at mucosal surfaces. Mucosal surfaces include the oronasal cavities, ocular surface, gastrointestinal tract, respiratory tract, and reproductive tract. Mucosal tissue-resident memory (TRM) CD4⁺ and CD8⁺ TRM cells serve as sentinels and critical mediators of adaptive mucosal immunity, continuously trafficking to mucosal tissues to surveil and clear invading pathogens. The development of mucosal CD4⁺ and CD8⁺ TRM cells is regulated by mechanisms distinct from those governing circulating effector memory (TEM) and central memory (TCM) T cells. Current models suggest that the generation, retention, and expansion of CD4⁺ and CD8⁺ TRM cells within mucosal tissues are coordinated by mucosa-specific chemokines and adhesion molecules, thereby facilitating their selective homing and retention at mucosal surfaces. Among the 48 known chemokines, CXCL17, CCL25, CCL28, and CXCL14 have emerged as major key mucosal-specific chemokines that orchestrate mucosal CD4⁺ and CD8⁺ TRM cell responses. This review (1) describes the roles of these four major mucosal chemokines in shaping TRM cell-mediated immunity against mucosal pathogens, with a focus on herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2), two infectious pathogens of the ocular and genital mucosae and (2) discuss harnessing these mucosal chemokine–receptor axes to develop a tissue-targeted Prime/Pull/Keep (PPK) herpes vaccine and immunotherapeutic strategies.
Keywords: CCL25, CCL28, Cellular immunity, Chemokines, CXCL14, CXCL17, memory CD4+ and CD8+ T cells, tissue-resident
Received: 08 Jul 2025; Accepted: 19 Jan 2026.
Copyright: © 2026 BENMOHAMED, Lekbach, Chentoufi, Prakash, Karan, Hormi-Carver, Dorotta and Quadiri. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: LBACHIR BENMOHAMED
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