Homing and cellular traffic in lymph nodes

Andrian, Ulrich H. von; Mempel, Thorsten R.

doi:10.1038/nri1222

Cited by 1,130 publications

(1,059 citation statements)

References 143 publications

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“…7C, D). This resembles the CK-addressin molecular system involved in CCR7 + /L-selectin + T and B cell recruitment to secondary lymphoid organs [29]. However, of considerable importance, PNAd + HEV in RA synovium did not reveal CCL21 endothelial production, as shown by IHC and ISH (Fig.…”

Section: Ccl21 In Situ Production and Microstructural Lymphoid Organimentioning

confidence: 60%

Systematic microanatomical analysis of CXCL13 and CCL21 in situ production and progressive lymphoid organization in rheumatoid synovitis

Paoletti²,

et al. 2005

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CXCL13 and CCL21 have been functionally implicated in lymphoid tissue organization both in the upstream phases of lymphoid tissue embryogenesis and in ectopic lymphoid neogenesis in transgenic mice. Here, we analyzed the relationship between CXCL13 and CCL21 production and lymphoid tissue organization in rheumatoid synovitis as a model of a naturally occurring ectopic lymphoneogenesis. Through systematic analysis of mRNA and protein expression, we defined the microanatomical relationship between CXCL13 and CCL21 in progressive aggregational and structural phases of synovial inflammatory infiltrate. We provide the first direct in situ evidence that production of CXCL13 and CCL21 (rather than simply protein binding) is associated with inflammatory lymphoid tissue formation and development with the demonstration, in organized aggregates, of a secondary lymphoid organ-like compartmentalization and vascular association. Notably, the presence of CXCL13 and CCL21 (protein and mRNA) was also demonstrated in non-organized clusters and minor aggregational stages, providing evidence that their induction can take place independently and possibly upstream of T-B compartmentalization, CD21 + follicular dendritic cell network differentiation and germinal center formation. Our data support the concept that, under inflammatory conditions, CXCL13 and CCL21 participate in lymphoid tissue microanatomical organization, attempting to recapitulate, in an aberrant lymphoid neogenetic process, their homeostatic and morphogenetic physiologic functions.

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Section: Ccl21 In Situ Production and Microstructural Lymphoid Organimentioning

confidence: 60%

Systematic microanatomical analysis of CXCL13 and CCL21 in situ production and progressive lymphoid organization in rheumatoid synovitis

Paoletti²,

et al. 2005

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“…To fulfill this task lymph nodes are situated in strategically unique locations between blood and lymphatic vascular structures. In order to interact with each other, lymphocytes extravasate across the HEV and APC enter via the subcapsular lymphatic sinus (summarized in [2]). The precise molecular mechanism involved in diapedesis of lymphocytes or APC across the endothelial cell wall of the respective vessels is not well understood.…”

Section: Discussionmentioning

confidence: 99%

“…The molecular mechanisms of the multi-step recruitment of lymphocytes via HEV are well characterized with the exception to the final diapedesis step [2]. It is generally assumed that naive lymphocytes move through HEV via a paracellular route through the junctions [22].…”

Section: Discussionmentioning

confidence: 99%

“…Arriving in the lymph node via the blood, naive lymphocytes extravasate at the level of highly specialized vascular endothelial cells of the post-capillary venules, the high endothelial venules (HEV) [1]. The endothelial cells of HEV display specific cell adhesion and signaling molecules, such as the peripheral lymph node addressin (PNAd), directing extravasation of naive lymphocytes across the vascular wall (summar-ized in [2]). In contrast, APC and soluble antigens arrive via afferent lymphatic vessels and enter the lymph node via the subcapsular sinus.…”

Section: Introductionmentioning

confidence: 99%

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Distinct molecular composition of blood and lymphatic vascular endothelial cell junctions establishes specific functional barriers within the peripheral lymph node

et al. 2008

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Lymph nodes are strategically localized at the interfaces between the blood and lymphatic vascular system, delivering immune cells and antigens to the lymph node. As cellular junctions of endothelial cells actively regulate vascular permeability and cell traffic, we have investigated their molecular composition by performing an extensive immunofluorescence study for adherens and tight junction molecules, including vascular endothelium (VE)-cadherin, the vascular claudins 1, 3, 5 and 12, occludin, members of the junctional adhesion molecule family plus endothelial cell-selective adhesion molecule (ESAM)-1, platelet endothelial cell adhesion molecule-1, ZO-1 and ZO-2. We found that junctions of high endothelial venules (HEV), which serve as entry site for naive lymphocytes, are unique due to their lack of the endothelial cell-specific claudin-5. LYVE-1 + sinus-lining endothelial cells form a diffusion barrier for soluble molecules that arrive at the afferent lymph and use claudin-5 and ESAM-1 to establish characteristic tight junctions. Analysis of the spatial relationship between the different vascular compartments revealed that HEV extend beyond the paracortex into the medullary sinuses, where they are protected from direct contact with the lymph by sinus-lining endothelial cells. The specific molecular architecture of cellular junctions present in blood and lymphatic vessel endothelium in peripheral lymph nodes establishes distinct barriers controlling the distribution of antigens and immune cells within this tissue.

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“…Chemokine receptor CXCR3 is essential for the physiologic and pathologic recruitment of plasmacytoid dendritic cell precursors, monocytes and natural killer cells to inflamed lymph nodes (LNs) (Cella et al, 1999;Janatpour et al, 2001;Martin-Fontecha et al, 2004), and for retention of Th1 lymphocytes within LNs (Yoneyama et al, 2002). On the other hand, chemokine receptor CCR7 plays a central role in the recruitment of naı¨ve T cells, some memory T cells, and mature dendritic cells to LNs (Cyster, 1999;von Andrian and Mempel, 2003). In contrast, the roles of chemokines in malignant tumors appear complex.…”

Section: Introductionmentioning

confidence: 99%

Chemokine receptor CXCR3 promotes colon cancer metastasis to lymph nodes

et al. 2007

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Chemokines and their receptors are essential for leukocyte trafficking, and also implicated in cancer metastasis to specific organs. We have recently demonstrated that CXCR3 plays a critical role in metastasis of mouse melanoma cells to lymph nodes. Here, we show that some human colon cancer cell lines express CXCR3 constitutively. We constructed cells that expressed CXCR3 cDNA ('DLD-1-CXCR3'), and compared with nonexpressing controls by rectal transplantation in nude mice. Although both cell lines disseminated to lymph nodes at similar frequencies at 2 weeks, DLD-1-CXCR3 expanded more rapidly than the control in 4 weeks. In 6 weeks, 59% of mice inoculated with DLD1-CXCR3 showed macroscopic metastasis in para-aortic lymph nodes, whereas only 14% of those with the control (Po0.05). In contrast, metastasis to the liver or lung was rare, and unaffected by CXCR3 expression. In clinical colon cancer samples, we found expression of CXCR3 in 34% cases, most of which had lymph node metastasis. Importantly, patients with CXCR3-positive cancer showed significantly poorer prognosis than those without CXCR3, or those expressing CXCR4 or CCR7. These results indicate that activation of CXCR3 with its ligands stimulates colon cancer metastasis preferentially to the draining lymph nodes with poorer prognosis.

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Homing and cellular traffic in lymph nodes

Cited by 1,130 publications

References 143 publications

Systematic microanatomical analysis of CXCL13 and CCL21 in situ production and progressive lymphoid organization in rheumatoid synovitis

Systematic microanatomical analysis of CXCL13 and CCL21 in situ production and progressive lymphoid organization in rheumatoid synovitis

Distinct molecular composition of blood and lymphatic vascular endothelial cell junctions establishes specific functional barriers within the peripheral lymph node

Chemokine receptor CXCR3 promotes colon cancer metastasis to lymph nodes

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