Migratory CD103+CD11b+ cDC2s in Peyer's patches are critical for gut IgA responses following oral immunization
Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved..
Induction and regulation of specific intestinal immunoglobulin (Ig)A responses critically depend on dendritic cell (DC) 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 cluster of differentiation (CD)103- conventional DC (cDC)2s and lysozyme-expressing DC (LysoDCs) in the subepithelial dome and of CD103+ cDC2s that expressed CD101 in the T cell zones, while oral ovalbumin (OVA) tolerization was instead associated with greater accumulation of cDC1s and peripherally induced regulatory T cells (pTregs) in this area. 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 OVA transgenic T cell receptor CD4 T cell adoptive transfer models, we found that co-transferred endogenous wildtype CD4 T cells can hinder the induction of OVA-specific IgA responses through secretion of interleukin-10. CT could overcome this blocking effect, apparently through a modulating effect on pTregs while promoting an expansion of follicular helper T cells. The data support a model where cDC1-induced pTreg normally suppresses PP responses for any given antigen and where CT's oral adjuvanticity effect is dependent on promoting follicular helper T cell responses through induction of CD103+ cDC2s.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2024 |
|---|---|
| Enthalten in: |
Mucosal immunology - (2024) vom: 15. März |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Gribonika, Inta [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
|---|
| Anmerkungen: |
Date Revised 05.04.2024 published: Print-Electronic Citation Status Publisher |
|---|
| doi: |
10.1016/j.mucimm.2024.03.004 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM36982427X |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM36982427X | ||
| 003 | DE-627 | ||
| 005 | 20240406232319.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240317s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.mucimm.2024.03.004 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1367.xml |
| 035 | |a (DE-627)NLM36982427X | ||
| 035 | |a (NLM)38492746 | ||
| 035 | |a (PII)S1933-0219(24)00023-0 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Gribonika, Inta |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Migratory CD103+CD11b+ cDC2s in Peyer's patches are critical for gut IgA responses following oral immunization |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Revised 05.04.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status Publisher | ||
| 520 | |a Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a Induction and regulation of specific intestinal immunoglobulin (Ig)A responses critically depend on dendritic cell (DC) 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 cluster of differentiation (CD)103- conventional DC (cDC)2s and lysozyme-expressing DC (LysoDCs) in the subepithelial dome and of CD103+ cDC2s that expressed CD101 in the T cell zones, while oral ovalbumin (OVA) tolerization was instead associated with greater accumulation of cDC1s and peripherally induced regulatory T cells (pTregs) in this area. 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 OVA transgenic T cell receptor CD4 T cell adoptive transfer models, we found that co-transferred endogenous wildtype CD4 T cells can hinder the induction of OVA-specific IgA responses through secretion of interleukin-10. CT could overcome this blocking effect, apparently through a modulating effect on pTregs while promoting an expansion of follicular helper T cells. The data support a model where cDC1-induced pTreg normally suppresses PP responses for any given antigen and where CT's oral adjuvanticity effect is dependent on promoting follicular helper T cell responses through induction of CD103+ cDC2s | ||
| 650 | 4 | |a Journal Article | |
| 700 | 1 | |a Strömberg, Anneli |e verfasserin |4 aut | |
| 700 | 1 | |a Chandode, Rakesh K |e verfasserin |4 aut | |
| 700 | 1 | |a Schön, Karin |e verfasserin |4 aut | |
| 700 | 1 | |a Lahl, Katharina |e verfasserin |4 aut | |
| 700 | 1 | |a Bemark, Mats |e verfasserin |4 aut | |
| 700 | 1 | |a Lycke, Nils |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Mucosal immunology |d 2008 |g (2024) vom: 15. März |w (DE-627)NLM185144039 |x 1935-3456 |7 nnns |
| 773 | 1 | 8 | |g year:2024 |g day:15 |g month:03 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.mucimm.2024.03.004 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |j 2024 |b 15 |c 03 | ||