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

Kazuki Nagashima, Shinichiro Sawa, Takeshi Nitta, Alejandro Prados, Vasiliki Koliaraki, George Kollias, Tomoki Nakashima, Hiroshi Takayanagi

Research output: Contribution to journalArticle

2 Citations (Scopus)

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/Δ Col6a1-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.

Original languageEnglish
Pages (from-to)437-443
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume493
Issue number1
DOIs
Publication statusPublished - Nov 4 2017
Externally publishedYes

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Helper-Inducer T-Lymphocytes
Tissue
Immunoglobulin A
Antigen-antibody reactions
Lymphoid Tissue
Endothelial cells
Bacteria
Genes
Cytokines
Cell Differentiation
Chemical analysis
Peyer's Patches
Symbiosis
Microbiota
Gene Deletion
Endothelial Cells

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Targeted deletion of RANKL in M cell inducer cells by the Col6a1-Cre driver. / Nagashima, Kazuki; Sawa, Shinichiro; Nitta, Takeshi; Prados, Alejandro; Koliaraki, Vasiliki; Kollias, George; Nakashima, Tomoki; Takayanagi, Hiroshi.

In: Biochemical and Biophysical Research Communications, Vol. 493, No. 1, 04.11.2017, p. 437-443.

Research output: Contribution to journalArticle

Nagashima, K, Sawa, S, Nitta, T, Prados, A, Koliaraki, V, Kollias, G, Nakashima, T & Takayanagi, H 2017, 'Targeted deletion of RANKL in M cell inducer cells by the Col6a1-Cre driver', Biochemical and Biophysical Research Communications, vol. 493, no. 1, pp. 437-443. https://doi.org/10.1016/j.bbrc.2017.09.004
Nagashima, Kazuki ; Sawa, Shinichiro ; Nitta, Takeshi ; Prados, Alejandro ; Koliaraki, Vasiliki ; Kollias, George ; Nakashima, Tomoki ; Takayanagi, Hiroshi. / Targeted deletion of RANKL in M cell inducer cells by the Col6a1-Cre driver. In: Biochemical and Biophysical Research Communications. 2017 ; Vol. 493, No. 1. pp. 437-443.
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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/Δ Col6a1-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.",
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