title: 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.
authors.affiliation: Mucosal Immunology Section, International Vaccine Institute, Seoul 151-818, South Korea.
authors.forename: Hye-Ran
authors.initials: HR
authors.lastname: Cha
authors.forename: Hyun-Jeong
authors.initials: HJ
authors.lastname: Ko
authors.forename: Eun-Do
authors.initials: ED
authors.lastname: Kim
authors.forename: Sun-Young
authors.initials: SY
authors.lastname: Chang
authors.forename: Sang-Uk
authors.initials: SU
authors.lastname: Seo
authors.forename: Nicolas
authors.initials: N
authors.lastname: Cuburu
authors.forename: Sangryeol
authors.initials: S
authors.lastname: Ryu
authors.forename: Sunghoon
authors.initials: S
authors.lastname: Kim
authors.forename: Mi-Na
authors.initials: MN
authors.lastname: Kweon
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D041702:BALB 3T3 Cells; D015153:Blotting, Western; D019742:Chemokines, CC / Q000096:biosynthesis* / Q000276:immunology; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D002772:Cholera Toxin / Q000008:administration & dosage / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D004967:Estrogens / Q000276:immunology* / Q000378:metabolism; D005260:Female; D018928:Immunity, Mucosal / Q000276:immunology*; D007071:Immunoglobulin A, Secretory / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D010950:Plasma Cells / Q000276:immunology* / Q000378:metabolism; D054447:Receptors, CCR10 / Q000276:immunology / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014599:Uterus / Q000276:immunology* / Q000378:metabolism; D014611:Vaccination
chemical_list: C511142:Ccl28 protein, mouse; C515707:Ccr10 protein, mouse; D019742:Chemokines, CC; D004967:Estrogens; D007071:Immunoglobulin A, Secretory; D054447:Receptors, CCR10; D010047:Ovalbumin; D002772:Cholera Toxin