Skin and gut imprinted helper T cell subsets exhibit distinct functional phenotypes in central nervous system autoimmunity.

Nature Immunology
Michael HiltenspergerThomas Korn

Abstract

Multidimensional single-cell analyses of T cells have fueled the debate about whether there is extensive plasticity or 'mixed' priming of helper T cell subsets in vivo. Here, we developed an experimental framework to probe the idea that the site of priming in the systemic immune compartment is a determinant of helper T cell-induced immunopathology in remote organs. By site-specific in vivo labeling of antigen-specific T cells in inguinal (i) or gut draining mesenteric (m) lymph nodes, we show that i-T cells and m-T cells isolated from the inflamed central nervous system (CNS) in a model of multiple sclerosis (MS) are distinct. i-T cells were Cxcr6+, and m-T cells expressed P2rx7. Notably, m-T cells infiltrated white matter, while i-T cells were also recruited to gray matter. Therefore, we propose that the definition of helper T cell subsets by their site of priming may guide an advanced understanding of helper T cell biology in health and disease.

References

Mar 6, 1992·Cell·P MombaertsV E Papaioannou
Nov 5, 1997·Trends in Neurosciences·N S FoulkesP Sassone-Corsi
Jul 7, 1998·The Journal of Experimental Medicine·T LitzenburgerA Iglesias
Sep 7, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·D UnutmazD R Littman
May 7, 2003·The Journal of Experimental Medicine·Estelle BettelliVijay K Kuchroo
Oct 16, 2004·Immunity·Makoto IwataSi-Young Song
Mar 18, 2005·Annual Review of Immunology·Mireia Sospedra, Roland Martin
Oct 4, 2005·Proceedings of the National Academy of Sciences of the United States of America·Aravind SubramanianJill P Mesirov
Sep 7, 2006·The Journal of Clinical Investigation·Gurumoorthy KrishnamoorthyAndreas Holz
Sep 7, 2006·The Journal of Clinical Investigation·Estelle BettelliVijay K Kuchroo
Jun 21, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Rajshekhar AlliTerrence L Geiger
Aug 20, 2008·Nature Immunology·Hekla Sigmundsdottir, Eugene C Butcher
Jan 10, 2009·Annual Review of Immunology·Thomas KornVijay K Kuchroo
Apr 14, 2009·Nature Methods·Gert-Jan KremersDavid W Piston
May 26, 2009·Immunity·Liang ZhouDan R Littman
Sep 3, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Phuong NguyenTerrence L Geiger
Dec 15, 2010·Current Protocols in Bioinformatics·Ben Langmead
Feb 1, 2011·Nature Immunology·Keiji HirotaBrigitta Stockinger
Oct 28, 2011·Nature·Kerstin BererGurumoorthy Krishnamoorthy
Jul 24, 2012·Genesis : the Journal of Genetics and Development·Anh H PhamDavid C Chan
Aug 8, 2012·Nature Reviews. Genetics·François Spitz, Eileen E M Furlong
Sep 11, 2012·Nature Immunology·Youjin LeeVijay K Kuchroo
May 7, 2014·Nature Communications·Christina HeinemannThomas Korn
Dec 6, 2014·Neuroimaging Clinics of North America·Stefan Dirk Roosendaal, Frederik Barkhof
Jun 5, 2015·Frontiers in Immunology·Björn RissiekSahil Adriouch
May 10, 2016·Scientific Reports·Swati ParekhInes Hellmann
May 12, 2016·Annual Review of Immunology·Federica Sallusto
Jul 19, 2017·Proceedings of the National Academy of Sciences of the United States of America·Nikolaos I KyratsousNaoto Kawakami
Oct 11, 2017·Nature Methods·Sara AibarStein Aerts
Dec 26, 2017·Lancet Neurology·Alan J ThompsonJeffrey A Cohen
Jul 6, 2018·Nature·Henrique Borges da SilvaStephen C Jameson
Aug 10, 2018·Nature·Gioele La MannoPeter V Kharchenko
Nov 6, 2018·Nature Communications·Joost SmoldersJörg Hamann

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Software Mentioned

annotatePeaks
NIS Elements AR
R
MeanVarPlot
R package scFunction
Regulatory Genomics Toolbox
R package velocyto
Seurat R package
HOMER
GraphPad Prism

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