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Migratory CD103+CD11b+ cDC2 cells in Peyer's patches are critical for gut IgA responses following oral immunization.

Gribonika, Inta ; Strömberg, Anneli ; Chandode, Rakesh K ; Schön, Karin ; Lahl, Katharina LU ; Bemark, Mats LU orcid and Lycke, Nils (2024) In Mucosal Immunology
Abstract

Induction and regulation of specific intestinal IgA responses critically depend on dendritic cell subsets and the T cells they activate in the Peyer's patches (PP). We found that oral immunization with cholera toxin (CT) as an adjuvant resulted in migration-dependent changes in the composition and localization of PP DC subsets with increased numbers of CD103 - cDC2s and LysoDCs in the subepithelial dome and of CD103 + cDC2s that expressed CD101 in the T cell zones (TZ), while oral OVA tolerization was instead associated with larger quantities of TZ cDC1s and pTregs. Decreased IgA responses were observed after CT adjuvanted immunization in huCD207DTA mice lacking CD103 + cDC2s, while oral OVA tolerization was inefficient in... (More)

Induction and regulation of specific intestinal IgA responses critically depend on dendritic cell subsets and the T cells they activate in the Peyer's patches (PP). We found that oral immunization with cholera toxin (CT) as an adjuvant resulted in migration-dependent changes in the composition and localization of PP DC subsets with increased numbers of CD103 - cDC2s and LysoDCs in the subepithelial dome and of CD103 + cDC2s that expressed CD101 in the T cell zones (TZ), while oral OVA tolerization was instead associated with larger quantities of TZ cDC1s and pTregs. Decreased IgA responses were observed after CT adjuvanted immunization in huCD207DTA mice lacking CD103 + cDC2s, while oral OVA tolerization was inefficient in cDC1-deficient Batf3 -/- mice. Using Ovalbumin (OVA) TCR transgenic CD4 T cell adoptive transfer models, we found that co-transferred endogenous WT CD4 T cells can hinder the induction of OVA-specific IgA responses through secretion of IL-10. CT could overcome this blocking effect, apparently through a modulating effect on peripherally induced Tregs (pTreg) while promoting an expansion of follicular helper T cells (Tfh). The data support a model where cDC1-induced pTreg normally supress PP responses for any given antigen and where CT's oral adjuvanticity effect is dependent on promoting Tfh responses through induction of CD103 + cDC2s.

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author
; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
epub
subject
keywords
IgA, oral immunization, cholera toxin, classical dendritic cells, peripherally induced regulatory T cells, Foxp3, follicular helper T cells, Peyer’s patches
in
Mucosal Immunology
pages
34 pages
publisher
Nature Publishing Group
external identifiers
  • scopus:85189662723
  • pmid:38492746
ISSN
1933-0219
DOI
10.1016/j.mucimm.2024.03.004
language
English
LU publication?
yes
id
99fad9b6-37ce-42a3-b893-4aa14d1a106b
date added to LUP
2024-03-20 10:36:42
date last changed
2024-04-26 14:29:03
@article{99fad9b6-37ce-42a3-b893-4aa14d1a106b,
  abstract     = {{<p>Induction and regulation of specific intestinal IgA responses critically depend on dendritic cell subsets and the T cells they activate in the Peyer's patches (PP). We found that oral immunization with cholera toxin (CT) as an adjuvant resulted in migration-dependent changes in the composition and localization of PP DC subsets with increased numbers of CD103 - cDC2s and LysoDCs in the subepithelial dome and of CD103 + cDC2s that expressed CD101 in the T cell zones (TZ), while oral OVA tolerization was instead associated with larger quantities of TZ cDC1s and pTregs. Decreased IgA responses were observed after CT adjuvanted immunization in huCD207DTA mice lacking CD103 + cDC2s, while oral OVA tolerization was inefficient in cDC1-deficient Batf3 -/- mice. Using Ovalbumin (OVA) TCR transgenic CD4 T cell adoptive transfer models, we found that co-transferred endogenous WT CD4 T cells can hinder the induction of OVA-specific IgA responses through secretion of IL-10. CT could overcome this blocking effect, apparently through a modulating effect on peripherally induced Tregs (pTreg) while promoting an expansion of follicular helper T cells (Tfh). The data support a model where cDC1-induced pTreg normally supress PP responses for any given antigen and where CT's oral adjuvanticity effect is dependent on promoting Tfh responses through induction of CD103 + cDC2s. </p>}},
  author       = {{Gribonika, Inta and Strömberg, Anneli and Chandode, Rakesh K and Schön, Karin and Lahl, Katharina and Bemark, Mats and Lycke, Nils}},
  issn         = {{1933-0219}},
  keywords     = {{IgA; oral immunization; cholera toxin; classical dendritic cells; peripherally induced regulatory T cells; Foxp3; follicular helper T cells; Peyer’s patches}},
  language     = {{eng}},
  month        = {{03}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Mucosal Immunology}},
  title        = {{Migratory CD103+CD11b+ cDC2 cells in Peyer's patches are critical for gut IgA responses following oral immunization.}},
  url          = {{http://dx.doi.org/10.1016/j.mucimm.2024.03.004}},
  doi          = {{10.1016/j.mucimm.2024.03.004}},
  year         = {{2024}},
}