Mucosal Chemokines

Abstract

Several chemokines have important functions in mucosal immunity. While there are many chemokines, 4 of them (CCL25, CCL28, CXCL14, and CXCL17) are especially important in mucosal immunity because they are homeostatically expressed in mucosal tissues. Of these, only CCL25 and CCL28 have been widely recognized as mucosal chemokines. In this study, we review the physiology of these chemokines with specific emphasis on their function in mucosal immunity. CCL25 recruits certain important subsets of T cells that express CCR9 to the small intestine. These CCR9 + T cells also express the integrin a4b7 and have been shown to play important roles in the control of intestinal inflammation. CCL28 recruits CCR10+ IgA plasmablasts to the lactating mammary gland. The role of CXCL14 in mucosal immunity is less well defined, but a Cxcl14 -/-mouse exhibits significant metabolic abnormalities. Finally, CXCL17 was the last chemokine to be described and signals through a new chemokine receptor (GPR35/CXCR8), which is expressed in a subset of macrophages that are recruited to mucosal tissues by this chemokine. We conclude that these 4 chemokines play very important roles in mucosal immunity and their continued functional characterization will likely identify novel therapeutic targets.

Cxcl17 -/- mice develop exacerbated disease in a T cell-dependent autoimmune model

“…The antimicrobial activity is not restricted to CXCL17; other chemokines including CXCL9, CXCL10, CXCL11, CXCL14, CCL25, and CCL28 have been shown to kill pathogens including gram‐negative and gram‐positive bacteria, parasites, and/or fungi . We should note, however, that the antimicrobial properties of mucosal homeostatic chemokines (CXCL14, CCL28, CCL25, and CXCL17) appear to be unique because they exhibit both prominent wide‐spectrum antimicrobial activity and also antifungal activity (especially against Candida albicans ) . This suggests that these mucosal chemokines have mucosal‐specific functions.…”

“…[37][38][39] We should note, however, that the antimicrobial properties of mucosal homeostatic chemokines (CXCL14, CCL28, CCL25, and CXCL17) appear to be unique because they exhibit both prominent wide-spectrum antimicrobial activity and also antifungal activity (especially against Candida albicans). 18 This suggests that these mucosal chemokines have mucosal-specific functions.…”

Intramuscular Immunization with Chemokine-Adjuvanted Inactive Porcine Epidemic Diarrhea Virus Induces Substantial Protection in Pigs

“…In pigs, similar abilities to recruit CCR9+ or CCR10+ cells and facilitate them homing to the mucosal sites have been demonstrated in porcine CCL25, 27 or 28 [18,26,30,37,42]. Differing from previous studies in using plasmid of CC chemokines as mucosal adjuvants in DNA vaccines [32,33,43], purified mammalian cells-derived porcine chemokines were used instead in the present study.…”

“…Moreover, pigs immunized with iPEDV in combination with CCL25 and CCL28 elicited substantial protection against a virulent PEDV challenge. We show that the porcine CC chemokines could be novel adjuvants for developing IM vaccines for modulating mucosal immune responses against mucosal transmissible pathogens in pigs.Vaccines 2020, 8, 102 2 of 16 immunization region to mucosal sites [25][26][27][28][29][30]. On the other hand, the CCL25/TECK expressed by mucosal epithelial cells can chemo-attract CCR9+ cells and support CCR9 expression leukocytes to migrate to the small intestine [30,31].…”

“…We show that the porcine CC chemokines could be novel adjuvants for developing IM vaccines for modulating mucosal immune responses against mucosal transmissible pathogens in pigs.Vaccines 2020, 8, 102 2 of 16 immunization region to mucosal sites [25][26][27][28][29][30]. On the other hand, the CCL25/TECK expressed by mucosal epithelial cells can chemo-attract CCR9+ cells and support CCR9 expression leukocytes to migrate to the small intestine [30,31]. The application of CCL27 and CCL25 as an adjuvant in DNA vaccines was proven to enhance systemic and/or mucosal immune responses following IM injection in mice or macaques [32,33].…”