The sphingosine 1-phosphate receptor 1 causes tissue retention by inhibiting the entry of peripheral tissue T lymphocytes into afferent lymphatics

Ledgerwood, Levi; Lal, Girdhari; Zhang, Nan; Garin, Alexandre; Esses, Steven J.; Ginhoux, Florent; Mérad, Miriam; Pêche, Hélène; Lira, Sérgio A.; Ding, Yaozhong; Yu, Yang; He, Xingxing; Schuchman, Edward H.; Allende, María L.; Ochando, Jordi; Bromberg, Jonathan S.

doi:10.1038/ni1534

Cited by 227 publications

(287 citation statements)

References 50 publications

Supporting

Mentioning

270

Contrasting

Unclassified

Order By: Relevance

“…In addition, lymphatic endothelial cell expression of macrophage mannose receptor (Marttila-Ichihara et al 2008) and CLEVER-1 (Salmi et al 2004) has been identiWed to mediate lymphocyte binding, although a role in DC migration has yet to be determined. Sphingosine-1-phosphate is required for T cell entry into lymphatics (Ledgerwood et al 2008), but its function in DC emigration is yet to be evaluated.…”

Section: Other Moleculesmentioning

confidence: 99%

Visualizing dendritic cell migration within the skin

Roediger

Smith

et al. 2008

Histochem Cell Biol

View full text Add to dashboard Cite

Dendritic cells (DCs) within the skin are a heterogeneous population of cells, including Langerhans cells of the epidermis and at least three subsets of dermal DCs. Collectively, these DCs play important roles in the initiation of adaptive immune responses following antigen challenge of the skin as well as being mediators of tolerance to self-antigen. A key functional aspect of cutaneous DCs is their migration both within the skin and into lymphatic vessels, resulting in their emigration to draining lymph nodes. Here, we discuss our current understanding of the requirements for successful DC migration in and from the skin, and introduce some of the microscopic techniques developed in our laboratory to facilitate a better understanding of this process. In particular, we detail our current use of multi-photon excitation (MPE) microscopy of murine skin to dissect the migratory behavior of DCs in vivo.

show abstract

Section: Other Moleculesmentioning

confidence: 99%

Visualizing dendritic cell migration within the skin

Roediger

Smith

et al. 2008

Histochem Cell Biol

View full text Add to dashboard Cite

show abstract

“…In line with this, Ccr7 2/2 effector CD8 T cells introduced into uninfected skin fail to exit the injection site and, consequently, show enhanced local conversion into CD69 + CD103 + T RM cells (3). Other migration molecules, such as the sphingosine-1-phosphate (S1P) receptor S1P 1 , have been implicated in the regulation of peripheral T cell accumulation and long-term retention, although its precise function in this process remains to be determined (10,12,13). Effector T cells use S1P 1 to sense S1P gradients among blood, tissues, and lymph, thereby guiding entry into efferent lymphatics during egress from lymphoid tissues (14).…”

mentioning

confidence: 95%

Cutting Edge: CD69 Interference with Sphingosine-1-Phosphate Receptor Function Regulates Peripheral T Cell Retention

Mackay

Braun

MacLeod

et al. 2015

The Journal of Immunology

389

387

View full text Add to dashboard Cite

Tissue-resident memory T cells provide local immune protection in barrier tissues, such as skin and mucosa. However, the molecular mechanisms controlling effector T cell retention and subsequent memory formation in those locations are not fully understood. In this study, we analyzed the role of CD69, an early leukocyte activation marker, in regulating effector T cell egress from peripheral tissues. We provide evidence that CD69 surface expression by skin-infiltrating CD8 T cells can be regulated at multiple levels, including local Ag stimulation and signaling through type I IFNRs, and it coincides with the transcriptional downregulation of the sphingosine-1-phosphate receptor S1P1. Importantly, we demonstrate that expression of CD69, by interfering with sphingosine-1-phosphate receptor function, is a critical determinant of prolonged T cell retention and local memory formation. Our results define an important step in the generation of long-lived adaptive immune memory at body surfaces.

show abstract

“…Molecules such as lymphatic vessel endothelial hyaluronan receptor-1 (Lyve-1), podoplanin, vascular endothelial growth factor receptor-3 (VEGFR-3), and prospero homeobox 1 (PROX1), which discriminate lymphatic from blood vessel endothelium are expressed at roughly comparable levels both on afferent and efferent lymphatics in human (2). Moreover, molecules known to participate in physiological cell trafficking such as sphingosine-1-phosphate receptor, macrophage mannose receptor, and Clever-1/ Stabilin-1 act both on the afferent and efferent arms of the lymphatic vasculature (3)(4)(5)(6). Functionally afferent and efferent lymphatics have a fundamental difference: most leukocytes can enter the LN via the afferent lymphatics, but only lymphocytes can exit the nodes via the efferent lymphatics under steady-state conditions.…”

mentioning

confidence: 99%

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

The sphingosine 1-phosphate receptor 1 causes tissue retention by inhibiting the entry of peripheral tissue T lymphocytes into afferent lymphatics

Cited by 227 publications

References 50 publications

Visualizing dendritic cell migration within the skin

Visualizing dendritic cell migration within the skin

Cutting Edge: CD69 Interference with Sphingosine-1-Phosphate Receptor Function Regulates Peripheral T Cell Retention

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

Contact Info

Product

Resources

About