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Biochem Biophys Res Commun. 2017 Nov 4;493(1):437-443. doi: 10.1016/j.bbrc.2017.09.004. Epub 2017 Sep 5.

Targeted deletion of RANKL in M cell inducer cells by the Col6a1-Cre driver.

Author information

1
Department of Immunology, Graduate School of Medicine and Faculty of Medicine, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo, 113-0033, Japan.
2
Division of Developmental Immunology, Institute for Genetic Medicine, Hokkaido University, Kita 15, Nishi 7, Kita-ku, Sapporo, 060-0815, Japan; Japan Agency for Medical Research and Development, Precursory Research for Innovative MEdical care (AMED-PRIME), Kita 15, Nishi 7, Kita-ku, Sapporo, 060-0815, Japan.
3
Division of Immunology, Biomedical Sciences Research Center 'Alexander Fleming', 34, Fleming Street, 16672, Vari, Attica, Greece.
4
Division of Immunology, Biomedical Sciences Research Center 'Alexander Fleming', 34, Fleming Street, 16672, Vari, Attica, Greece; Department of Experimental Physiology, School of Medicine, National and Kapodistrian University of Athens, 75 Mikras Asias Street, 11527, Goudi, Athens, Greece.
5
Department of Cell Signaling, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Yushima 1-5-45, Bunkyo-ku, Tokyo, 113-8549, Japan; Japan Science and Technology Agency (JST), Precursory Research for Embryonic Science and Technology (PRESTO), Yushima 1-5-45, Bunkyo-ku, Tokyo, 113-8549, Japan; Japan Agency for Medical Research and Development, Core Research for Evolutional Science and Technology (AMED-CREST), Yushima 1-5-45, Bunkyo-ku, Tokyo, 113-8549, Japan.
6
Department of Immunology, Graduate School of Medicine and Faculty of Medicine, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo, 113-0033, Japan. Electronic address: takayana@m.u-tokyo.ac.jp.

Abstract

The gut-associated lymphoid tissues (GALTs), including Peyer's patches (PPs), cryptopatches (CPs) and isolated lymphoid follicles (ILFs), establish a host-microbe symbiosis by the promotion of immune reactions against gut microbes. Microfold cell inducer (MCi) cells in GALTs are the recently identified mesenchymal cells that express the cytokine RANKL and initiate bacteria-specific immunoglobulin A (IgA) production via induction of microfold (M) cell differentiation. In the previous study, the Twist2-Cre driver was utilized for gene deletion in mesenchymal cells including MCi cells. In order to investigate MCi cells more extensively, it will be necessary to develop experimental tools in addition to the Twist2-Cre driver mice and characterize such drivers in specificity and efficiency. Here we show that M cell differentiation and IgA production are impaired in the targeted deletion of RANKL by the Col6a1-Cre driver. We compared Col6a1-Cre with Twist2-Cre in terms of the specificity for mesenchymal cells in GALTs. Col6a1-Cre CAG-CAT-EGFP mice exhibited EGFP expression in podoplanin+CD31- cells including MCi cells, while Twist2-Cre mice were shown to target endothelial cells and podoplanin+CD31- cells. Tnfsf11fl/ΔCol6a1-Cre mice exhibited the absence of M cells and severe IgA reduction together with an alteration in gut microbial composition. Moreover, we analyzed germ free mice to test whether changes in the microbiota are the cause of M cell deficiency. M cell differentiation was normal in the CPs/ILFs of germ free mice, indicating that MCi cells induce M cells independently of microbial colonization. This study demonstrates that Col6a1-Cre driver mice are as useful as Twist2-Cre driver mice for functional analyses of GALT-resident mesenchymal cells, including MCi cells.

KEYWORDS:

IgA; M cell inducer cells; Mesenchymal stromal cells; Peyer's patch; The gut microbiota

PMID:
28882590
DOI:
10.1016/j.bbrc.2017.09.004
[Indexed for MEDLINE]

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