Afferent lymph–derived T cells and DCs use different chemokine receptor CCR7–dependent routes for entry into the lymph node and intranodal migration

Braun, Asolina; Worbs, Tim; Moschovakis, Georgios Leandros; Halle, Stephan; Hoffmann, Katharina; Bölter, Jasmin; Münk, Anika; Förster, Reinhold

doi:10.1038/ni.2085

Cited by 288 publications

(304 citation statements)

References 37 publications

Supporting

Mentioning

293

Contrasting

Order By: Relevance

“…3A), but not on cortical or subcortical LS. This is well in line with the report of Braun et al (19) who found that lymphocytes directly infused into the afferent lymphatics enter the lymph nodes preferentially via the medullary sinus, but use the SS when injected together with dendritic cells.…”

Section: Discussionsupporting

confidence: 80%

Gene-expression profiling of different arms of lymphatic vasculature identifies candidates for manipulation of cell traffic

Iftakhar-E-Khuda

Fair-Mäkelä

Kukkonen-Macchi

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Afferent lymphatic vessels bring antigens and diverse populations of leukocytes to draining lymph nodes, whereas efferent lymphatics allow only lymphocytes and antigens to leave the nodes. Despite the fundamental importance of afferent vs. efferent lymphatics in immune response and cancer spread, the molecular characteristics of these different arms of the lymphatic vasculature are largely unknown. The objective of this work was to explore molecular differences behind the distinct functions of afferent and efferent lymphatic vessels, and find possible molecules mediating lymphocyte traffic. We used laser-capture microdissection and cell sorting to isolate lymphatic endothelial cells (LECs) from the subcapsular sinus (SS, afferent) and lymphatic sinus (LS, efferent) for transcriptional analyses. The results reveal marked differences between afferent and efferent LECs and identify molecules on lymphatic vessels. Further characterizations of Siglec-1 (CD169) and macrophage scavenger receptor 1 (MSR1/CD204), show that they are discriminatively expressed on lymphatic endothelium of the SS but not on lymphatic vasculature of the LS. In contrast, endomucin (EMCN) is present on the LS endothelium and not on lymphatic endothelium of the SS. Moreover, both murine and human MSR1 on lymphatic endothelium of the SS bind lymphocytes and in in vivo studies MSR1 regulates entrance of lymphocytes from the SS to the lymph node parenchyma. In conclusion, this paper reports surprisingly distinct molecular profiles for afferent and efferent lymphatics and a function for MSR1. These results may open avenues to explore some of the now-identified molecules as targets to manipulate the function of lymphatic vessels.lymphatics | cell traffic | lymphocytes | endothelium

show abstract

Section: Discussionsupporting

confidence: 80%

Gene-expression profiling of different arms of lymphatic vasculature identifies candidates for manipulation of cell traffic

Iftakhar-E-Khuda

Fair-Mäkelä

Kukkonen-Macchi

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…Here, we considered the novel possibility that the development of an expanded network of lymphatics in and around fibrosarcomas might facilitate entry of naïve T cells from neighboring tissues via afferent lymph. In support of this hypothesis, naïve T cells have been reported in afferent lymph, albeit in lower numbers than memory cells 17. Uptake of lymph into fibrosarcomas was assessed by monitoring the accumulation of Evans Blue Dye,18 after injection of the dye into the base of the leg of a tumor‐bearing mouse (Supporting Information Fig.…”

Section: Resultsmentioning

confidence: 95%

Progression of carcinogen‐induced fibrosarcomas is associated with the accumulation of naïve CD4+ T cells via blood vessels and lymphatics

Ondondo

Jones

Hindley

et al. 2013

Intl Journal of Cancer

View full text Add to dashboard Cite

The tumor microenvironment comprises newly formed blood and lymphatic vessels which shape the influx, retention and departure of lymphocytes within the tumor mass. Thus, by influencing the intratumoral composition of lymphocytes, these vessels affect the manner in which the adaptive immune system responds to the tumor, either promoting or impairing effective antitumor immunity. In our study, we utilized a mouse model of carcinogen‐induced fibrosarcoma to examine the composition of tumor‐infiltrating lymphocytes during tumor progression. In particular, we sought to determine whether CD4+Foxp3+ regulatory T cells (Tregs) became enriched during tumor progression thereby contributing to tumor‐driven immunosuppression. This was not the case as the proportion of Tregs and effector CD4+ T cells actually declined within the tumor owing to the unexpected accumulation of naïve T cells. However, we found no evidence for antigen‐driven migration of these T cells or for their participation in an antitumor immune response. Our data support the notion that lymphocytes can enter tumors via aberrantly formed blood and lymphatic vessels. Such findings suggest that targeting both the tumor vasculature and lymphatics will alter the balance of lymphocyte subpopulations that enter the tumor mass. A consideration of this aspect of tumor immunology may be critical to the success of solid cancer immunotherapies.

show abstract

“…In contrast, cortical and medullary sinuses contained T cells (data not shown) and B cells but not DCs (Fig. 6Aiii, 6Av), because very few DCs egress from LNs compared with lymphocytes (7,10,15,37,38). Because few DCs from noninflamed skin migrate to the LNs, we induced DC migration by epicutaneous application of a contact sensitizer.…”

Section: Preferential Expansion Of Cortical and Medullary Sinuses Occmentioning

confidence: 93%

Expansion of Cortical and Medullary Sinuses Restrains Lymph Node Hypertrophy during Prolonged Inflammation

Tan

Yeo

Wong

et al. 2012

The Journal of Immunology

View full text Add to dashboard Cite

During inflammation, accumulation of immune cells in activated lymph nodes (LNs), coupled with a transient shutdown in lymphocyte exit, results in dramatic cellular expansion. Counter-regulatory measures to restrain LN expansion must exist and may include re-establishment of lymphocyte egress to steady-state levels. Indeed, we show in a murine model that egress of lymphocytes from LNs was returned to steady-state levels during prolonged inflammation following initial retention. This restoration in lymphocyte egress was supported by a preferential expansion of cortical and medullary sinuses during late inflammation. Cortical and medullary sinus remodeling during late inflammation was dependent on temporal and spatial changes in vascular endothelial growth factor-A distribution. Specifically, its expression was restricted to the subcapsular space of the LN during early inflammation, whereas its expression was concentrated in the paracortical and medullary regions of the LN at later stages. We next showed that this process was mostly driven by the synergistic cross-talk between fibroblastic reticular cells and interstitial flow. Our data shed new light on the biological significance of LN lymphangiogenesis during prolonged inflammation and further underscore the collaborative roles of stromal cells, immune cells, and interstitial flow in modulating LN plasticity and function.

show abstract

Afferent lymph–derived T cells and DCs use different chemokine receptor CCR7–dependent routes for entry into the lymph node and intranodal migration

Cited by 288 publications

References 37 publications

Gene-expression profiling of different arms of lymphatic vasculature identifies candidates for manipulation of cell traffic

Gene-expression profiling of different arms of lymphatic vasculature identifies candidates for manipulation of cell traffic

Progression of carcinogen‐induced fibrosarcomas is associated with the accumulation of naïve CD4+ T cells via blood vessels and lymphatics

Expansion of Cortical and Medullary Sinuses Restrains Lymph Node Hypertrophy during Prolonged Inflammation

Contact Info

Product

Resources

About