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CollagenVI-Cre mice: A new tool to target stromal cells in secondary lymphoid organs

View Article: PubMed Central - PubMed

ABSTRACT

Stromal cells in secondary lymphoid organs (SLOs) are non-hematopoietic cells involved in the regulation of adaptive immune responses. Three major stromal populations have been identified in adult SLOs: fibroblastic reticular cells (FRCs), follicular dendritic cells (FDCs) and marginal reticular cells (MRCs). The properties of these individual populations are not clearly defined, mainly due to the lack of appropriate genetic tools, especially for MRCs. Here, we analyzed stromal cell targeting in SLOs from a transgenic mouse strain that expresses Cre recombinase under the CollagenVI promoter, using lineage tracing approaches. We show that these mice target specifically MRCs and FDCs, but not FRCs in Peyer’s patches and isolated lymphoid follicles in the intestine. In contrast, stromal cells in lymph nodes and the spleen do not express the transgene, which renders ColVI-cre mice ideal for the specific targeting of stromal cells in the gut-associated lymphoid tissue (GALT). This funding further supports the hypothesis of organ-specific stromal precursors in SLOs. Interestingly, in all tissues analyzed, there was also high specificity for perivascular cells, which have been proposed to act as FDC precursors. Taken together, ColVI-Cre mice are a useful new tool for the dissection of MRC- and FDC-specific functions and plasticity in the GALT.

No MeSH data available.


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ColVI-Cre targets MRCs and FDCs in ILFs.Representative images of immature (iILFs) and mature ILFs (mILFs), showing Cre-mediated GFP expression. B cells are marked as B220+ cells, MRCs as MAdCAM-1+ networks, and FDCs as CD35+ networks. Inserts display higher magnification of selected areas. Scale bars, 75 μm. Several ILFs from 5 different transgenic mice were analyzed.
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f3: ColVI-Cre targets MRCs and FDCs in ILFs.Representative images of immature (iILFs) and mature ILFs (mILFs), showing Cre-mediated GFP expression. B cells are marked as B220+ cells, MRCs as MAdCAM-1+ networks, and FDCs as CD35+ networks. Inserts display higher magnification of selected areas. Scale bars, 75 μm. Several ILFs from 5 different transgenic mice were analyzed.

Mentions: PPs are part of the GALT along with isolated lymphoid follicles (ILFs). ILFs were described relatively recently as single B-cell aggregates with an architecture and cellular composition similar to PPs3233. They develop postnatally and their size and composition depends on external stimuli and commensal bacteria, producing a spectrum of appearances ranging from small B cell clusters (immature ILFs) to well-organized lymphoid structures containing germinal centers (mature ILFs)34. Apart from B and T-cells they also include stromal cells, which are still poorly characterized. Using ColVI-Cre-Rosa26mT/mG mice, we further identified GFP expression inside both immature and mature ILFs, which co-localized with MAdCAM-1 and CD35 expression, marking MRCs and FDCs, respectively (Fig. 3). We also observed a continuous GFP+ network that connects the intestinal and ILF stroma, suggesting a close relationship between the two cell populations. Together, these results indicate that ColVI-Cre mice may be used to target particular stromal subsets in the GALT and could help to elucidate both their specific functions and their potential ontogenetic relationships.


CollagenVI-Cre mice: A new tool to target stromal cells in secondary lymphoid organs
ColVI-Cre targets MRCs and FDCs in ILFs.Representative images of immature (iILFs) and mature ILFs (mILFs), showing Cre-mediated GFP expression. B cells are marked as B220+ cells, MRCs as MAdCAM-1+ networks, and FDCs as CD35+ networks. Inserts display higher magnification of selected areas. Scale bars, 75 μm. Several ILFs from 5 different transgenic mice were analyzed.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5015111&req=5

f3: ColVI-Cre targets MRCs and FDCs in ILFs.Representative images of immature (iILFs) and mature ILFs (mILFs), showing Cre-mediated GFP expression. B cells are marked as B220+ cells, MRCs as MAdCAM-1+ networks, and FDCs as CD35+ networks. Inserts display higher magnification of selected areas. Scale bars, 75 μm. Several ILFs from 5 different transgenic mice were analyzed.
Mentions: PPs are part of the GALT along with isolated lymphoid follicles (ILFs). ILFs were described relatively recently as single B-cell aggregates with an architecture and cellular composition similar to PPs3233. They develop postnatally and their size and composition depends on external stimuli and commensal bacteria, producing a spectrum of appearances ranging from small B cell clusters (immature ILFs) to well-organized lymphoid structures containing germinal centers (mature ILFs)34. Apart from B and T-cells they also include stromal cells, which are still poorly characterized. Using ColVI-Cre-Rosa26mT/mG mice, we further identified GFP expression inside both immature and mature ILFs, which co-localized with MAdCAM-1 and CD35 expression, marking MRCs and FDCs, respectively (Fig. 3). We also observed a continuous GFP+ network that connects the intestinal and ILF stroma, suggesting a close relationship between the two cell populations. Together, these results indicate that ColVI-Cre mice may be used to target particular stromal subsets in the GALT and could help to elucidate both their specific functions and their potential ontogenetic relationships.

View Article: PubMed Central - PubMed

ABSTRACT

Stromal cells in secondary lymphoid organs (SLOs) are non-hematopoietic cells involved in the regulation of adaptive immune responses. Three major stromal populations have been identified in adult SLOs: fibroblastic reticular cells (FRCs), follicular dendritic cells (FDCs) and marginal reticular cells (MRCs). The properties of these individual populations are not clearly defined, mainly due to the lack of appropriate genetic tools, especially for MRCs. Here, we analyzed stromal cell targeting in SLOs from a transgenic mouse strain that expresses Cre recombinase under the CollagenVI promoter, using lineage tracing approaches. We show that these mice target specifically MRCs and FDCs, but not FRCs in Peyer’s patches and isolated lymphoid follicles in the intestine. In contrast, stromal cells in lymph nodes and the spleen do not express the transgene, which renders ColVI-cre mice ideal for the specific targeting of stromal cells in the gut-associated lymphoid tissue (GALT). This funding further supports the hypothesis of organ-specific stromal precursors in SLOs. Interestingly, in all tissues analyzed, there was also high specificity for perivascular cells, which have been proposed to act as FDC precursors. Taken together, ColVI-Cre mice are a useful new tool for the dissection of MRC- and FDC-specific functions and plasticity in the GALT.

No MeSH data available.


Related in: MedlinePlus