Cutting Edge: JAM-C Controls Homeostatic Chemokine Secretion in Lymph Node Fibroblastic Reticular Cells Expressing Thrombomodulin

Frontera, Vincent; Arcangeli, Marie-Laure; Zimmerli, Claudia; Bardin, Florence; Obrados, Elodie; Audebert, Stéphane; Bajénoff, Marc; Borg, Jean-Paul; Aurrand-Lions, Michel

doi:10.4049/jimmunol.1003441

Cited by 15 publications

(14 citation statements)

References 22 publications

(18 reference statements)

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“…This finding implies that the currently used FRC phenotype description (Pdpn + CD31 − ) may obscure the true diversity of stromal cells in SLOs. This interpretation has been confirmed in a recent study that defines a particular FRC subpopulation through JAM-C controlled chemokine secretion (Frontera et al, 2011). Using genetic tools such as BAC transgenic mouse lines with stromal cell-specific promoters will help to define both function and phenotype of SLO stromal cells in future studies.…”

Section: Discussionsupporting

confidence: 61%

A novel bacterial artificial chromosome-transgenic Podoplanin–Cre mouse targets lymphoid organ stromal cells in vivo

et al. 2011

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Stromal cells provide the structural foundation of secondary lymphoid organs (SLOs), and regulate leukocyte access and cell migration within the different compartments of spleen and lymph nodes (LNs). Furthermore, several stromal cell subsets have been implied in shaping of T cell responses through direct presentation of antigen. Despite significant gain of knowledge on the biology of different SLO-resident stromal cell subsets, their molecular and functional characterization has remained incomplete. To address this need, we have generated a bacterial artificial chromosome-transgenic mouse model that utilizes the podoplanin (pdpn) promoter to express the Cre-recombinase exclusively in stromal cells of SLOs. The characterization of the Pdpn–Cre mouse revealed transgene expression in subsets of fibroblastic reticular cells and lymphatic endothelial cells in LNs. Furthermore, the transgene facilitated the identification of a novel splenic perivascular stromal cell subpopulation that forms web-like structures around central arterioles. Assessment of the in vivo antigen expression in the genetically tagged stromal cells in Pdpn–Cre mice revealed activation of both MHC I and II-restricted TCR transgenic T cells. Taken together, stromal pdpn–Cre expression is well-suited to characterize the phenotype and to dissect the function of lymphoid organ stromal cells.

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Section: Discussionsupporting

confidence: 61%

A novel bacterial artificial chromosome-transgenic Podoplanin–Cre mouse targets lymphoid organ stromal cells in vivo

et al. 2011

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“…As chemokines are in part synthesized by lymphoid stromal cells including FRCs, CCL21 detected in tissue sections could be preferentially localized inside FRC conduits for transport to the HEV network, where it may contribute to lymphocyte recruitment. [30][31][32][33][34] Thus, 2-P microscopy imaging helps to uncouple in vitro chemoattractant responsiveness from in vivo chemoattractant responsiveness, which depends on the "usable" chemokine levels available to trafficking lymphocytes. At the same time, these data highlight the importance of chemokine receptor levels in responding to presumably limited amounts of stromal chemokine.…”

Section: Discussionmentioning

confidence: 99%

Naive B-cell trafficking is shaped by local chemokine availability and LFA-1–independent stromal interactions

Coelho

Natale

Soriano

et al. 2013

Blood

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Key Points• CXCR5, but not CXCR4 or CCR7, acts with LFA-1 to mediate random B-cell migration in the T-cell area and B-cell follicles.• In contrast, stromal guidance during B-cell migration is LFA-1 independent and CXCR5 independent.It is not known how naive B cells compute divergent chemoattractant signals of the T-cell area and B-cell follicles during in vivo migration. Here, we used two-photon microscopy of peripheral lymph nodes (PLNs) to analyze the prototype G-protein-coupled receptors (GPCRs) CXCR4, CXCR5, and CCR7 during B-cell migration, as well as the integrin LFA-1 for stromal guidance. CXCR4 and CCR7 did not influence parenchymal B-cell motility and distribution, despite their role during B-cell arrest in venules. In contrast, CXCR5 played a nonredundant role in B-cell motility in follicles and in the T-cell area. B-cell migration in the T-cell area followed a random guided walk model, arguing against directed migration in vivo. LFA-1, but not a4 integrins, contributed to B-cell motility in PLNs. However, stromal network guidance was LFA-1 independent, uncoupling integrin-dependent migration from stromal attachment. Finally, we observed that despite a 20-fold reduction of chemokine expression in virus-challenged PLNs, CXCR5 remained essential for B-cell screening of antigen-presenting cells. Our data provide an overview of the contribution of prototype GPCRs and integrins during naive B-cell migration and shed light on the local chemokine availability that these cells compute. (Blood. 2013;121(20):4101-4109)

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“…More recently, Frontera et al. found that a subset of thrombomodulin‐expressing FRCs coexpressed JAM‐C in murine lymph nodes. The authors reported that this subpopulation of FRCs expressed the highest levels of mRNA for CCL19, CCL21a, and CXCL12.…”

Section: Contact‐dependent Regulation Of Stromal Cell Functionmentioning

confidence: 99%

Stromal and hematopoietic cells in secondary lymphoid organs: partners in immunity

Malhotra

Fletcher

Turley

2012

Immunological Reviews

137

123

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Summary Secondary lymphoid organs (SLOs), including lymph nodes, Peyer's patches, and the spleen, have evolved to bring cells of the immune system together. In these collaborative environments, lymphocytes scan the surfaces of antigen-presenting cells for cognate antigens, while moving along stromal networks. The cell-cell interactions between stromal and hematopoietic cells in SLOs are therefore integral to the normal functioning of these tissues. Not only do stromal cells physically construct SLO architecture, but they are essential for regulating hematopoietic populations within these domains. Stromal cells interact closely with lymphocytes and dendritic cells, providing scaffolds on which these cells migrate, and recruiting them into niches by secreting chemokines. Within lymph nodes, stromal cell-ensheathed conduit networks transport small antigens deep into the SLO parenchyma. More recently, stromal cells have been found to induce peripheral CD8+ T-cell tolerance and control the extent to which newly activated T cells proliferate within lymph nodes. Thus, stromal-hematopoietic crosstalk has important consequences for regulating immune cell function within SLOs. In addition, stromal cell interactions with hematopoietic cells, other stroma, and the inflammatory milieu have profound effects on key stromal functions. Here, we examine ways in which these interactions within the lymph node environment influence the adaptive immune response.

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Cutting Edge: JAM-C Controls Homeostatic Chemokine Secretion in Lymph Node Fibroblastic Reticular Cells Expressing Thrombomodulin

Cited by 15 publications

References 22 publications

A novel bacterial artificial chromosome-transgenic Podoplanin–Cre mouse targets lymphoid organ stromal cells in vivo

A novel bacterial artificial chromosome-transgenic Podoplanin–Cre mouse targets lymphoid organ stromal cells in vivo

Naive B-cell trafficking is shaped by local chemokine availability and LFA-1–independent stromal interactions

Stromal and hematopoietic cells in secondary lymphoid organs: partners in immunity

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