Mucosa-Associated Epithelial Chemokine/CCL28 Expression in the Uterus Attracts CCR10+ IgA Plasma Cells following Mucosal Vaccination via Estrogen Control

Abstract

Previous studies demonstrated cross talk between mucosal and reproductive organs during secretory IgA Ab induction. In this study, we aimed to clarify the underlying mechanisms of this cross talk. We found significantly higher titers of Ag-specific secretory IgA Ab in the vaginal wash after mucosal vaccination by both the intranasal (i.n.) and the intravaginal routes but not by the s.c. route. Interestingly, Ag-specific IgA Ab-secreting cells (ASCs) were found mainly in the uterus but not in the cervix and vaginal canal after i.n. vaccination. The fact that most Ag-specific IgA ASCs isolated from the uteri of vaccinated mice migrated toward mucosa-associated epithelial chemokine (MEC)/CCL28 suggests dominant expression of CCR10 on the IgA ASCs. Further, IgA ASCs in the uteri of vaccinated mice were reduced drastically in mice treated with neutralizing anti-MEC/CCL28 Ab. Most intriguingly, the female sex hormone estrogen directly regulated MEC/CCL28 expression and was augmented by i.n. vaccination with cholera toxin or stimulators for innate immunity. Further, blockage of estrogen function in the uterus by oral administration of the estrogen antagonist raloxifene significantly inhibited migration of Ag-specific IgA ASCs after i.n. vaccination with OVA plus cholera toxin. Taken together, these data strongly suggest that CCR10+ IgA ASCs induced by mucosal vaccination via the i.n. route migrate into the uterus in a MEC/CCL28-dependent manner and that estrogen might have a crucial role in the protection against genital infection by regulating MEC/CCL28 expression in the uterus.

A Colanic Acid Operon Deletion Mutation Enhances Induction of Early Antibody Responses by Live Attenuated Salmonella Vaccine Strains

“…However, the vaginal IgA is from both systemic and local production (97). The IgA levels in the genital tract are subject to a strong hormonal control that regulates the transportation of immunoglobulins, the level of cytokines, the distribution of various cell populations, and antigen presentation during the reproductive cycle as well as a compartmentalization of the immune response within the genital tract (97,98). All these factors may affect the level of IgA at a given time point.…”

Delivery strategies to enhance oral vaccination against enteric infections

“…This is thought to be the reason why vaccine administration at sites other than the mucosa is generally ineffective at promoting mucosal immunity [36]. The imprinting of gut homing molecules on lymphocytes by DCs is dependent on retinoic acid [76][77][78]. Upon antigen encounter, CD103 + DCs undergo maturation which allows them to migrate to the MLNs, initiating adaptive immune responses [73] ( Fig.…”

The Regulation of IgA Production

“…This is achieved by particular combinations of specific combinations of chemokine receptors (CCR9, CCR10, CXCR3, CXCR4) and adhesion molecules (α4β7 and α4β1) that are programmed at the same time as mucosal IgA induction (Bowman et al, 2002;Lazarus et al, 2003;Hieshima et al, 2004;Jaimes et al, 2004;Wilson and Butcher, 2004;Mora et al, 2006;Mora and Von Andrian, 2008;Morteau et al, 2008;Cha et al, 2011;Agnello et al, 2013).…”