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Title:
PD-L1 signaling selectively regulates T cell lymphatic transendothelial migration | Nature Communications
Description:
Programmed death-1 (PD-1) and its ligand PD-L1 are checkpoint molecules which regulate immune responses. Little is known about their functions in T cell migration and there are contradictory data about their roles in regulatory T cell (Treg) function. Here we show activated Tregs and CD4 effector T cells (Teffs) use PD-1/PD-L1 and CD80/PD-L1, respectively, to regulate transendothelial migration across lymphatic endothelial cells (LECs). Antibody blockade of Treg PD-1, Teff CD80 (the alternative ligand for PD-L1), or LEC PD-L1 impairs Treg or Teff migration in vitro and in vivo. PD-1/PD-L1 signals through PI3K/Akt and ERK to regulate zipper junctional VE-cadherin, and through NFκB-p65 to up-regulate VCAM-1 expression on LECs. CD80/PD-L1 signaling up-regulates VCAM-1 through ERK and NFκB-p65. PD-1 and CD80 blockade reduces tumor egress of PD-1high fragile Tregs and Teffs into draining lymph nodes, respectively, and promotes tumor regression. These data provide roles for PD-L1 in cell migration and immune regulation. The Programmed death-1 (PD-1) and its ligand PD-L1 are critical checkpoints in the regulation of immune responses. Here the authors implicate PD-L1 signalling at lymphatic endothelium in the regulation of transendothelial migration of T cells.
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Keywords {🔍}
pdl, cells, fig, pubmed, lecs, teffs, cell, tregs, article, migration, tem, expression, google, scholar, itregs, cas, blockade, lec, treg, central, tils, human, mouse, data, teff, tumor, antimouse, supplementary, dlns, blocking, signaling, activated, mice, endothelial, flow, nature, lymphatic, mab, inhibited, igg, erk, antipd, cytometry, expressed, increased, analysis, pdpdl, panel, regulatory, vecadherin,
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il-2 + anti-cd3/28 + tgf-β1-induced foxp3gfp+cd44highcd25+cd4+ itregs nature portfolio foxp3gfp−cd25−cd4+cd44low naïve cd4 crispr/cas9-knockout pd-l1−/− lecs privacy policy genome-wide libraries foxp3gfp+cd25+cd44low cd4+ ttregs anti-cd3/cd28 mab-dynabeads foxp3gfp+cd25+cd4+cd44high itregs 5 μg/ml anti-mouse pd-l1 advertising research cd4+cd25−cd127+cd45ra+ teffs 1 μg/ml anti-pd-l1 ab human cd4+cd25highcd127−cd45ra− tregs ifnγ+t-bet+pd-1+cd25−tregs author information authors immature bone-marrow-derived dc foxp3gfp+cd44lowcd25+cd4+ ttregs sorted foxp3gfp−cd25+cd4+teffs pd-1highcd25−foxp3+cd4 tregs pd-1highcd25-foxp3+cd4 tregs cd4+cd25-cd127+cd45ra+ fitc anti-mouse t-bet cd80-driven pd-l1 signaling pd-1/pd-l1 interactions revealed 20 ng/ml anti-mouse il-4 2 μg/ml anti-mouse pd-1 apc anti-mouse pd-l1 1 μg/ml pd-l1 ig anti-mouse pd-l1 mab 5 μg/ml anti-human pd-1 anti-human pd-l1 mab nature 439 nature suggesting pd-1/pd-l1 signals apc anti-human/mouse granzyme rat anti-mouse pd-l1 reprints suggesting pd-1/pd-l1 signaling plate-bound anti-cd3ɛ mab high-affinity fc receptor pd-l1 knockout mice cd25+foxp3gfp+cd4+ itregs foxp3+cd25−cd4 tregs cd25+foxp3+cd4 tregs cd25+foxp3+ cd4 tregs foxp3gfp−cd25+cd4+ teffs cd25−foxp3+ cd4 tregs38 foxp3gfp+cd25+cd44highcd4+ itregs
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headline:PD-L1 signaling selectively regulates T cell lymphatic transendothelial migration
description:Programmed death-1 (PD-1) and its ligand PD-L1 are checkpoint molecules which regulate immune responses. Little is known about their functions in T cell migration and there are contradictory data about their roles in regulatory T cell (Treg) function. Here we show activated Tregs and CD4 effector T cells (Teffs) use PD-1/PD-L1 and CD80/PD-L1, respectively, to regulate transendothelial migration across lymphatic endothelial cells (LECs). Antibody blockade of Treg PD-1, Teff CD80 (the alternative ligand for PD-L1), or LEC PD-L1 impairs Treg or Teff migration in vitro and in vivo. PD-1/PD-L1 signals through PI3K/Akt and ERK to regulate zipper junctional VE-cadherin, and through NFκB-p65 to up-regulate VCAM-1 expression on LECs. CD80/PD-L1 signaling up-regulates VCAM-1 through ERK and NFκB-p65. PD-1 and CD80 blockade reduces tumor egress of PD-1high fragile Tregs and Teffs into draining lymph nodes, respectively, and promotes tumor regression. These data provide roles for PD-L1 in cell migration and immune regulation. The Programmed death-1 (PD-1) and its ligand PD-L1 are critical checkpoints in the regulation of immune responses. Here the authors implicate PD-L1 signalling at lymphatic endothelium in the regulation of transendothelial migration of T cells.
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type:PostalAddress
type:Organization
name:University of Maryland School of Medicine
address:
name:Department of Surgery, University of Maryland School of Medicine, Baltimore, USA
type:PostalAddress
type:Organization
name:Vikas Saxena
url:http://orcid.org/0000-0003-4816-4875
affiliation:
name:Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine
address:
name:Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, USA
type:PostalAddress
type:Organization
name:University of Maryland School of Medicine
address:
name:Department of Surgery, University of Maryland School of Medicine, Baltimore, USA
type:PostalAddress
type:Organization
name:Jegan Iyyathurai
affiliation:
name:Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine
address:
name:Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, USA
type:PostalAddress
type:Organization
name:Ram Lakhan
affiliation:
name:Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine
address:
name:Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, USA
type:PostalAddress
type:Organization
name:University of Maryland School of Medicine
address:
name:Department of Surgery, University of Maryland School of Medicine, Baltimore, USA
type:PostalAddress
type:Organization
name:Yigang Zhang
affiliation:
name:Division of Blood & Marrow Transplant & Cellular Therapy, Department of Pediatrics, University of Minnesota Cancer Center
address:
name:Division of Blood & Marrow Transplant & Cellular Therapy, Department of Pediatrics, University of Minnesota Cancer Center, Minneapolis, USA
type:PostalAddress
type:Organization
name:Isadora Tadeval Lape
affiliation:
name:Center for Transplantation Sciences, Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts
address:
name:Center for Transplantation Sciences, Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts, Boston, USA
type:PostalAddress
type:Organization
name:Christina Paluskievicz
affiliation:
name:University of Maryland School of Medicine
address:
name:Department of Surgery, University of Maryland School of Medicine, Baltimore, USA
type:PostalAddress
type:Organization
name:Keli L. Hippen
affiliation:
name:Division of Blood & Marrow Transplant & Cellular Therapy, Department of Pediatrics, University of Minnesota Cancer Center
address:
name:Division of Blood & Marrow Transplant & Cellular Therapy, Department of Pediatrics, University of Minnesota Cancer Center, Minneapolis, USA
type:PostalAddress
type:Organization
name:Young Lee
affiliation:
name:University of Maryland School of Medicine
address:
name:Department of Surgery, University of Maryland School of Medicine, Baltimore, USA
type:PostalAddress
type:Organization
name:Emma Silverman
affiliation:
name:Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine
address:
name:Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, USA
type:PostalAddress
type:Organization
name:Marina W. Shirkey
affiliation:
name:Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine
address:
name:Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, USA
type:PostalAddress
type:Organization
name:Leonardo V. Riella
affiliation:
name:Center for Transplantation Sciences, Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts
address:
name:Center for Transplantation Sciences, Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts, Boston, USA
type:PostalAddress
type:Organization
name:Bruce R. Blazar
affiliation:
name:Division of Blood & Marrow Transplant & Cellular Therapy, Department of Pediatrics, University of Minnesota Cancer Center
address:
name:Division of Blood & Marrow Transplant & Cellular Therapy, Department of Pediatrics, University of Minnesota Cancer Center, Minneapolis, USA
type:PostalAddress
type:Organization
name:Jonathan S. Bromberg
affiliation:
name:Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine
address:
name:Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, USA
type:PostalAddress
type:Organization
name:University of Maryland School of Medicine
address:
name:Department of Surgery, University of Maryland School of Medicine, Baltimore, USA
type:PostalAddress
type:Organization
name:University of Maryland School of Medicine
address:
name:Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, USA
type:PostalAddress
type:Organization
email:[email protected]
PostalAddress:
name:Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, USA
name:Department of Surgery, University of Maryland School of Medicine, Baltimore, USA
name:Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, USA
name:Department of Surgery, University of Maryland School of Medicine, Baltimore, USA
name:Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, USA
name:Department of Surgery, University of Maryland School of Medicine, Baltimore, USA
name:Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, USA
name:Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, USA
name:Department of Surgery, University of Maryland School of Medicine, Baltimore, USA
name:Division of Blood & Marrow Transplant & Cellular Therapy, Department of Pediatrics, University of Minnesota Cancer Center, Minneapolis, USA
name:Center for Transplantation Sciences, Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts, Boston, USA
name:Department of Surgery, University of Maryland School of Medicine, Baltimore, USA
name:Division of Blood & Marrow Transplant & Cellular Therapy, Department of Pediatrics, University of Minnesota Cancer Center, Minneapolis, USA
name:Department of Surgery, University of Maryland School of Medicine, Baltimore, USA
name:Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, USA
name:Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, USA
name:Center for Transplantation Sciences, Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts, Boston, USA
name:Division of Blood & Marrow Transplant & Cellular Therapy, Department of Pediatrics, University of Minnesota Cancer Center, Minneapolis, USA
name:Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, USA
name:Department of Surgery, University of Maryland School of Medicine, Baltimore, USA
name:Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, USA
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- What's the income generated by https://scholar.google.co.uk/scholar?as_q=&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_sauthors=%22Jegan%20Iyyathurai%22&as_publication=&as_ylo=&as_yhi=&as_allsubj=all&hl=en each month?
- How much does https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=search&term=Ram%20Lakhan make?
- See how much https://scholar.google.co.uk/scholar?as_q=&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_sauthors=%22Ram%20Lakhan%22&as_publication=&as_ylo=&as_yhi=&as_allsubj=all&hl=en makes per month
- Check the income stats for https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=search&term=Yigang%20Zhang
- What's the revenue for https://scholar.google.co.uk/scholar?as_q=&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_sauthors=%22Yigang%20Zhang%22&as_publication=&as_ylo=&as_yhi=&as_allsubj=all&hl=en?
- Find out how much https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=search&term=Isadora%20Tadeval%20Lape earns monthly
- How profitable is https://scholar.google.co.uk/scholar?as_q=&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_sauthors=%22Isadora%20Tadeval%20Lape%22&as_publication=&as_ylo=&as_yhi=&as_allsubj=all&hl=en?
- What's the monthly income of https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=search&term=Christina%20Paluskievicz?
- How much profit is https://scholar.google.co.uk/scholar?as_q=&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_sauthors=%22Christina%20Paluskievicz%22&as_publication=&as_ylo=&as_yhi=&as_allsubj=all&hl=en making per month?
- What are the earnings of https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=search&term=Keli%20L.%20Hippen?
- What's the financial intake of https://scholar.google.co.uk/scholar?as_q=&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_sauthors=%22Keli%20L.%20Hippen%22&as_publication=&as_ylo=&as_yhi=&as_allsubj=all&hl=en?
- What's the total monthly financial gain of https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=search&term=Young%20Lee?
- https://scholar.google.co.uk/scholar?as_q=&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_sauthors=%22Young%20Lee%22&as_publication=&as_ylo=&as_yhi=&as_allsubj=all&hl=en income
- https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=search&term=Emma%20Silverman's financial summary
- See how much https://scholar.google.co.uk/scholar?as_q=&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_sauthors=%22Emma%20Silverman%22&as_publication=&as_ylo=&as_yhi=&as_allsubj=all&hl=en makes per month
- How much revenue does https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=search&term=Marina%20W.%20Shirkey generate?
- How much does https://scholar.google.co.uk/scholar?as_q=&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_sauthors=%22Marina%20W.%20Shirkey%22&as_publication=&as_ylo=&as_yhi=&as_allsubj=all&hl=en rake in every month?
- https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=search&term=Leonardo%20V.%20Riella's financial summary
- How much does https://scholar.google.co.uk/scholar?as_q=&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_sauthors=%22Leonardo%20V.%20Riella%22&as_publication=&as_ylo=&as_yhi=&as_allsubj=all&hl=en gross monthly?
- How much does https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=search&term=Bruce%20R.%20Blazar earn?
- What's the profit of https://scholar.google.co.uk/scholar?as_q=&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_sauthors=%22Bruce%20R.%20Blazar%22&as_publication=&as_ylo=&as_yhi=&as_allsubj=all&hl=en?
- https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=search&term=Jonathan%20S.%20Bromberg's revenue stream
- What are the total earnings of https://scholar.google.co.uk/scholar?as_q=&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_sauthors=%22Jonathan%20S.%20Bromberg%22&as_publication=&as_ylo=&as_yhi=&as_allsubj=all&hl=en?
- https://static-content.springer.com/esm/art%3A10.1038%2Fs41467-022-29930-0/MediaObjects/41467_2022_29930_MOESM1_ESM.pdf's revenue stream
- https://static-content.springer.com/esm/art%3A10.1038%2Fs41467-022-29930-0/MediaObjects/41467_2022_29930_MOESM2_ESM.pdf's financial summary
- What's the monthly money flow for https://static-content.springer.com/esm/art%3A10.1038%2Fs41467-022-29930-0/MediaObjects/41467_2022_29930_MOESM3_ESM.pdf?
- How much does https://static-content.springer.com/esm/art%3A10.1038%2Fs41467-022-29930-0/MediaObjects/41467_2022_29930_MOESM4_ESM.zip earn?
- http://creativecommons.org/licenses/by/4.0/ income
- Revenue of https://s100.copyright.com/AppDispatchServlet?title=PD-L1%20signaling%20selectively%20regulates%20T%20cell%20lymphatic%20transendothelial%20migration&author=Wenji%20Piao%20et%20al&contentID=10.1038%2Fs41467-022-29930-0©right=The%20Author%28s%29&publication=2041-1723&publicationDate=2022-04-21&publisherName=SpringerNature&orderBeanReset=true&oa=CC%20BY
- What's the income of https://crossmark.crossref.org/dialog/?doi=10.1038/s41467-022-29930-0?
- How much income is https://citation-needed.springer.com/v2/references/10.1038/s41467-022-29930-0?format=refman&flavour=citation earning monthly?
- What is the earnings of https://doi.org/10.1038/s41577-025-01149-2?
- https://doi.org/10.1038/s41575-024-00996-z's total income per month
- How much revenue does https://doi.org/10.1007/s42114-025-01295-0 bring in?
- How much cash flow does https://doi.org/10.1186/s12943-024-02023-w have monthly?
- What's https://www.protocols.io/'s gross income?
- How much money does https://www.natureindex.com/ generate?
- Revenue of http://www.naturechina.com
- Income figures for https://www.natureasia.com/ja-jp
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