Lymphatic endothelial S1P promotes mitochondrial function and survival in naive T cells

Mendoza, Alejandra; Fang, Victoria; Chen, Cynthia; Serasinghe, Madhavika N.; Verma, Akanksha; Muller, James; Chaluvadi, Venkata; Dustin, Michael L.; Hla, Timothy; Elemento, Olivier; Chipuk, Jerry E.; Schwab, Susan R.

doi:10.1038/nature22352

Cited by 157 publications

(160 citation statements)

References 32 publications

(35 reference statements)

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“…As a transporter of S1P, SPNS2 plays an important role in the release and function of S1P . SPNS2‐induced S1P secretion is necessary for naïve T cell circulation and survival, which is beneficial for adaptive immune responses, but it may contribute to autoreactive and malignant cell survival . It was found that SPNS2 level was decreased in advanced lung cancer cells.…”

Section: Discussionmentioning

confidence: 99%

SPNS2 promotes the malignancy of colorectal cancer cells via regulating Akt and ERK pathway

Jiang

Wang

et al. 2019

Clin Exp Pharma Physio

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Colorectal cancer (CRC) is a prevalent malignant tumour that causes considerable cancer‐related deaths globally. The sphingolipid transporter 2 (SPNS2), a sphingosine‐1‐phosphate (S1P) transporter, modulates multiple biological events including malignancy of cancer cells. In this study, the effects of SPNS2 on CRC progression were studied. We found that SPNS2 expression was significantly upregulated in CRC tissues compared to that in adjacent non‐tumour tissues. To assess the role of SPNS2 in CRC cells, we performed loss‐ and gain‐of‐function experiments in SW480 and HCT116 cells, respectively. The results demonstrated that SPNS2 promoted proliferation, migration and invasion, and inhibited apoptosis in CRC cells. Additionally, SPNS2 enhanced the release of intracellular S1P, and increased S1P receptor 1 (S1PR1) and S1PR3 expression. Moreover, SPNS2 activated the Akt and ERK pathways, and the biological behaviours of SPNS2 were attenuated by Akt or ERK inhibitor in HCT116 cells. In conclusion, our results demonstrated that SPNS2 promoted proliferation, migration and invasion, and inhibited apoptosis by regulating S1P/S1PR1/3 axis and activating Akt and ERK pathway in CRC cells.

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Section: Discussionmentioning

confidence: 99%

SPNS2 promotes the malignancy of colorectal cancer cells via regulating Akt and ERK pathway

Jiang

Wang

et al. 2019

Clin Exp Pharma Physio

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“…Treatment with FTY720 restricts the migration of circulating cells, so a stable population of Trm cells in treated mice demonstrates that these cells are neither replenished by, nor lost to, circulating populations 15, 17, 40. However, FTY720 may also inhibit egress of cells from peripheral tissues to draining lymph nodes and/or reduce cell survival 35, 41, 42, 43. Despite these potential caveats, results from FTY720‐treated animals reflect those from more elegant parabiosis experiments that demonstrate that Trm cells are a distinct population neither leaving the tissue nor being replenished by circulating cells 17, 30…”

Section: Memory Cd4 T‐cells Are Found Throughout the Bodymentioning

confidence: 99%

The roles of resident, central and effector memory CD4 T‐cells in protective immunity following infection or vaccination

2018

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SummaryImmunological memory provides rapid protection to pathogens previously encountered through infection or vaccination. CD4 T‐cells play a central role in all adaptive immune responses. Vaccines must, therefore, activate CD4 T‐cells if they are to generate protective immunity. For many diseases, we do not have effective vaccines. These include human immunodeficiency virus (HIV), tuberculosis and malaria, which are responsible for many millions of deaths each year across the globe. CD4 T‐cells play many different roles during the immune response coordinating the actions of many other cells. In order to harness the diverse protective effects of memory CD4 T‐cells, we need to understand how memory CD4 T‐cells are generated and how they protect the host. Here we review recent findings on the location of different subsets of memory CD4 T‐cells that are found in peripheral tissues (tissue resident memory T‐cells) and in the circulation (central and effector memory T‐cells). We discuss the generation of these cells, and the evidence that demonstrates how they provide immune protection in animal and human challenge models.

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“…These observations support a model in which pMHC-TCR contacts in peripheral lymphoid organs drive tonic signals in T cells that decay when they enter the circulation, and reappear when they return to lymphoid organs, in a cyclical pattern (Figure 2). In the circulation, T cells may receive different tonic signals, such as from S1P produced by lymphatic endothelial cells, which was recently shown to promote T cell survival in the circulation by maintaining T cell mitochondrial function [54]. …”

Section: The Early Days Of Tonic Signals In T Cells: What Is Their Fumentioning

confidence: 99%

Tonic Signals: Why Do Lymphocytes Bother?

Myers

Zikherman

Roose

2017

Trends in Immunology

100

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Since the 1990s it has been known that B- and T- lymphocytes exhibit low-level, constitutive signaling in the basal state (“tonic signaling”). These lymphocytes display a range of affinity for self, which generates a scale of tonic signaling. Surprisingly, what signaling pathways are active in the basal state and the functional relevance of the observed tonic signaling heterogeneity remain open questions today. Here we summarize what is known about the mechanistic and functional details of tonic signaling. We highlight recent advances that have increased our understanding of how the amount of tonic signal impacts immune function, describing novel tools that have moved the field forward and towards molecular understanding of tonic signaling.

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Lymphatic endothelial S1P promotes mitochondrial function and survival in naive T cells

Cited by 157 publications

References 32 publications

SPNS2 promotes the malignancy of colorectal cancer cells via regulating Akt and ERK pathway

SPNS2 promotes the malignancy of colorectal cancer cells via regulating Akt and ERK pathway

The roles of resident, central and effector memory CD4 T‐cells in protective immunity following infection or vaccination

Tonic Signals: Why Do Lymphocytes Bother?

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