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Mucosal Immunol. 2020 Mar 11. doi: 10.1038/s41385-020-0276-8. [Epub ahead of print]

αvβ8 integrin-expression by BATF3-dependent dendritic cells facilitates early IgA responses to Rotavirus.

Author information

1
Immunology Section, Lund University, 221 48, Lund, Sweden.
2
CIRI, Centre International de Recherche en Infectiologie, Univ Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, F-69007, Lyon, France.
3
Division of Biopharma, Institute for Health Technology, Technical University of Denmark (DTU), 2800, Kongens Lyngby, Denmark.
4
Berlin Institute of Health, BIH Innovations, 10178, Berlin, Germany.
5
Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Université Paris-Sud, INRA, Université Paris-Saclay, Gif-sur-Yvette Cedex, France.
6
Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université, INSERM, CNRS UMR, Marseille 13288, France; Centre d'Immunophénomique, Aix Marseille Université, INSERM, CNRS, Marseille, 13288, France.
7
Departments of Medicine and Immunology and Microbiology, Stanford University School of Medicine, Stanford, CA, 94305, USA.
8
VA Palo Alto Health Care System, Palo Alto, CA, 94304, USA.
9
CIRI, Centre International de Recherche en Infectiologie, Univ Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, F-69007, Lyon, France. helena.paidassi@inserm.fr.
10
Immunology Section, Lund University, 221 48, Lund, Sweden. Katharina.lahl@med.lu.se.
11
Division of Biopharma, Institute for Health Technology, Technical University of Denmark (DTU), 2800, Kongens Lyngby, Denmark. Katharina.lahl@med.lu.se.

Abstract

Secretory intestinal IgA can protect from re-infection with rotavirus (RV), but very little is known about the mechanisms that induce IgA production during intestinal virus infections. Classical dendritic cells (cDCs) in the intestine can facilitate both T cell-dependent and -independent secretory IgA. Here, we show that BATF3-dependent cDC1, but not cDC2, are critical for the optimal induction of RV-specific IgA responses in the mesenteric lymph nodes. This depends on the selective expression of the TGFβ-activating integrin αvβ8 by cDC1. In contrast, αvβ8 on cDC1 is dispensible for steady state immune homeostasis. Given that cDC2 are crucial in driving IgA during steady state but are dispensable for RV-specific IgA responses, we propose that the capacity of DC subsets to induce intestinal IgA responses reflects the context, as opposed to an intrinsic property of individual DC subsets.

PMID:
32161355
DOI:
10.1038/s41385-020-0276-8

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