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Peyer's patch T H17 cells are dispensable for gut IgA responses to oral immunization.

Gribonika, Inta ; Strömberg, Anneli ; Lebrero-Fernandez, Cristina ; Schön, Karin ; Moon, James ; Bemark, Mats LU orcid and Lycke, Nils (2022) In Science Immunology 7(73). p.1-14
Abstract

T helper 17 (T
H17) cells located at the Peyer's patch (PP) inductive site and at the lamina propria effector site of the intestinal immune system are responsive to both pathogenic and commensal bacteria. Their plasticity to convert into follicular helper T (T
FH) cells has been proposed to be central to gut immunoglobulin A (IgA) responses. Here, we used an IL-17A fate reporter mouse and an MHC-II tetramer to analyze antigen-specific CD4
+ T cell subsets and isolate them for single-cell RNA sequencing after oral immunization with cholera toxin and ovalbumin. We found a T
FH-dominated response with only rare antigen-specific T
H17 cells (<8%) in the PP. A clonotypic analysis provided little support that... (More)

T helper 17 (T
H17) cells located at the Peyer's patch (PP) inductive site and at the lamina propria effector site of the intestinal immune system are responsive to both pathogenic and commensal bacteria. Their plasticity to convert into follicular helper T (T
FH) cells has been proposed to be central to gut immunoglobulin A (IgA) responses. Here, we used an IL-17A fate reporter mouse and an MHC-II tetramer to analyze antigen-specific CD4
+ T cell subsets and isolate them for single-cell RNA sequencing after oral immunization with cholera toxin and ovalbumin. We found a T
FH-dominated response with only rare antigen-specific T
H17 cells (<8%) in the PP. A clonotypic analysis provided little support that clonotypes were shared between T
FH and T
H17 cells, arguing against T
H17 plasticity as a major contributor to T
FH differentiation. Two mouse models of T
H17 deficiency confirmed that gut IgA responses to oral immunization do not require T
H17 cells, with
CD4
CreRorc
fl/fl
mice exhibiting normal germinal centers in PP and unperturbed total IgA production in the intestine.

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author
; ; ; ; ; and
publishing date
type
Contribution to journal
publication status
published
keywords
Animals, Antigens/immunology, Cholera Toxin, Immunization, Immunoglobulin A/immunology, Mice, Peyer's Patches/cytology, Th17 Cells/immunology, Vaccination
in
Science Immunology
volume
7
issue
73
article number
eabc5500
pages
1 - 14
publisher
American Association for the Advancement of Science (AAAS)
external identifiers
  • scopus:85134084143
  • pmid:35776804
ISSN
2470-9468
DOI
10.1126/sciimmunol.abc5500
language
English
LU publication?
no
id
04b72c64-6570-4512-927d-e46be30a94ef
date added to LUP
2023-11-16 12:37:09
date last changed
2024-04-14 17:42:07
@article{04b72c64-6570-4512-927d-e46be30a94ef,
  abstract     = {{<p>T helper 17 (T<br>
 H17) cells located at the Peyer's patch (PP) inductive site and at the lamina propria effector site of the intestinal immune system are responsive to both pathogenic and commensal bacteria. Their plasticity to convert into follicular helper T (T<br>
 FH) cells has been proposed to be central to gut immunoglobulin A (IgA) responses. Here, we used an IL-17A fate reporter mouse and an MHC-II tetramer to analyze antigen-specific CD4<br>
 + T cell subsets and isolate them for single-cell RNA sequencing after oral immunization with cholera toxin and ovalbumin. We found a T<br>
 FH-dominated response with only rare antigen-specific T<br>
 H17 cells (&lt;8%) in the PP. A clonotypic analysis provided little support that clonotypes were shared between T<br>
 FH and T<br>
 H17 cells, arguing against T<br>
 H17 plasticity as a major contributor to T<br>
 FH differentiation. Two mouse models of T<br>
 H17 deficiency confirmed that gut IgA responses to oral immunization do not require T<br>
 H17 cells, with <br>
 CD4<br>
 CreRorc<br>
 fl/fl<br>
 mice exhibiting normal germinal centers in PP and unperturbed total IgA production in the intestine.<br>
 </p>}},
  author       = {{Gribonika, Inta and Strömberg, Anneli and Lebrero-Fernandez, Cristina and Schön, Karin and Moon, James and Bemark, Mats and Lycke, Nils}},
  issn         = {{2470-9468}},
  keywords     = {{Animals; Antigens/immunology; Cholera Toxin; Immunization; Immunoglobulin A/immunology; Mice; Peyer's Patches/cytology; Th17 Cells/immunology; Vaccination}},
  language     = {{eng}},
  number       = {{73}},
  pages        = {{1--14}},
  publisher    = {{American Association for the Advancement of Science (AAAS)}},
  series       = {{Science Immunology}},
  title        = {{Peyer's patch T
        H17 cells are dispensable for gut IgA responses to oral immunization.}},
  url          = {{http://dx.doi.org/10.1126/sciimmunol.abc5500}},
  doi          = {{10.1126/sciimmunol.abc5500}},
  volume       = {{7}},
  year         = {{2022}},
}