Fibroblastic reticular cell-derived lysophosphatidic acid regulates confined intranodal T-cell motility

ELife
Akira TakedaEiji Umemoto

Abstract

Lymph nodes (LNs) are highly confined environments with a cell-dense three-dimensional meshwork, in which lymphocyte migration is regulated by intracellular contractile proteins. However, the molecular cues directing intranodal cell migration remain poorly characterized. Here we demonstrate that lysophosphatidic acid (LPA) produced by LN fibroblastic reticular cells (FRCs) acts locally to LPA2 to induce T-cell motility. In vivo, either specific ablation of LPA-producing ectoenzyme autotaxin in FRCs or LPA2 deficiency in T cells markedly decreased intranodal T cell motility, and FRC-derived LPA critically affected the LPA2-dependent T-cell motility. In vitro, LPA activated the small GTPase RhoA in T cells and limited T-cell adhesion to the underlying substrate via LPA2. The LPA-LPA2 axis also enhanced T-cell migration through narrow pores in a three-dimensional environment, in a ROCK-myosin II-dependent manner. These results strongly suggest that FRC-derived LPA serves as a cell-extrinsic factor that optimizes T-cell movement through the densely packed LN reticular network.

References

May 5, 1997·FEBS Letters·M OkabeY Nishimune
Jun 19, 2002·Biochimica Et Biophysica Acta·Mei Chuan HuangEdward J Goetzl
Aug 2, 2003·Nature Reviews. Cancer·Gordon B Mills, Wouter H Moolenaar
Dec 12, 2003·Nature Reviews. Immunology·Ulrich H von Andrian, Thorsten R Mempel
May 4, 2004·Nature Reviews. Immunology·Masayuki Miyasaka, Toshiyuki Tanaka
Sep 8, 2004·Cytometry. Part a : the Journal of the International Society for Analytical Cytology·Martijn A NolteReina E Mebius
Sep 11, 2004·Immunity·Cenk SumenUlrich H von Andrian
Jun 24, 2005·Blood·Naotoshi KanemitsuMasayuki Miyasaka
Jun 20, 2006·Molecular and Cellular Biology·Laurens A van MeeterenJos Jonkers
Feb 22, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Takaharu Okada, Jason G Cyster
Feb 28, 2007·The Journal of Experimental Medicine·Tim WorbsReinhold Förster
Jun 6, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Julie H HuangMichael L Dustin
Nov 21, 2007·Nature Immunology·Susan R Schwab, Jason G Cyster
May 3, 2008·Nature·Tim LämmermannMichael Sixt
Sep 27, 2008·The American Journal of Pathology·Tae NakasakiMasayuki Miyasaka
Jan 22, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Zhongbin BaiMasayuki Miyasaka
Feb 10, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jordan JacobelliMatthew F Krummel
Jan 9, 2010·Annual Review of Pharmacology and Toxicology·Ji Woong ChoiJerold Chun
Sep 28, 2010·Blood·Mustapha FaroudiVictor L J Tybulewicz
Jan 18, 2011·Nature Structural & Molecular Biology·Hiroshi NishimasuOsamu Nureki
May 6, 2011·Critical Reviews in Immunology·Eiji UmemotoMasayuki Miyasaka
Jul 29, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Silvia F SorianoJens V Stein
Sep 15, 2011·Nature Reviews. Molecular Cell Biology·Wouter H Moolenaar, Anastassis Perrakis
Oct 6, 2011·The Journal of Biological Chemistry·Hiroshi YukiuraJunken Aoki
Feb 22, 2012·Journal of Visualized Experiments : JoVE·H L Rachel LiouAlex Y Huang
Aug 21, 2012·Biochimica Et Biophysica Acta·Keisuke YanagidaSatoshi Ishii
Sep 11, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Yafeng ZhangSteven D Rosen
Sep 29, 2012·Nature Reviews. Immunology·Jean-Philippe GirardReinhold Förster
Oct 17, 2012·Proceedings of the National Academy of Sciences of the United States of America·Judith N MandlRonald N Germain
Feb 1, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Zhongbin BaiMasayuki Miyasaka
Jul 3, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Tomoya KatakaiTatsuo Kinashi
Feb 28, 2014·Seminars in Immunopathology·Tim Lämmermann, Ronald N Germain
Jun 18, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Tomoya KatakaiTatsuo Kinashi
Jul 9, 2014·PloS One·Sara A KnowldenSteve N Georas
Feb 14, 2015·Cell·Verena RuprechtCarl-Philipp Heisenberg

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Citations

Jun 1, 2016·Frontiers in Immunology·Tomoya Katakai, Tatsuo Kinashi
Apr 18, 2017·Proceedings of the Japan Academy. Series B, Physical and Biological Sciences·Akira TakedaMasayuki Miyasaka
Apr 13, 2019·Immunological Reviews·Tim Lämmermann, Wolfgang Kastenmüller
Apr 13, 2019·Immunological Reviews·Christian Perez-ShibayamaBurkhard Ludewig
Apr 13, 2019·Immunological Reviews·Jens V Stein, Nora Ruef
Nov 9, 2018·Frontiers in Immunology·Mario NovkovicBurkhard Ludewig
Jun 6, 2017·Acta Neuropathologica Communications·K SchmitzI Tegeder
Sep 1, 2019·Journal of Autoimmunity·Christiana MagkriotiVassilis Aidinis
Feb 1, 2020·Biochimica Et Biophysica Acta. Molecular and Cell Biology of Lipids·Seung-Jae KimGye Young Park
Aug 1, 2021·Cell Biochemistry and Biophysics·Steve N Georas

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Methods Mentioned

BETA
GTPase
PCR
flow cytometry
confocal microscopy
pull-down
FCS
Assay

Software Mentioned

Metamorph
ImageJ
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Imaris
BioMap
GraphPad
Prism

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