The macrophage migration inhibitory factor pathway in human B cells is tightly controlled and dysregulated in multiple sclerosis

European Journal of Immunology
Liza RijversMarvin M van Luijn

Abstract

In MS, B cells survive peripheral tolerance checkpoints to mediate local inflammation, but the underlying molecular mechanisms are relatively underexplored. In mice, the MIF pathway controls B-cell development and the induction of EAE. Here, we found that MIF and MIF receptor CD74 are downregulated, while MIF receptor CXCR4 is upregulated in B cells from early onset MS patients. B cells were identified as the main immune subset in blood expressing MIF. Blocking of MIF and CD74 signaling in B cells triggered CXCR4 expression, and vice versa, with separate effects on their proinflammatory activity, proliferation, and sensitivity to Fas-mediated apoptosis. This study reveals a new reciprocal negative regulation loop between CD74 and CXCR4 in human B cells. The disturbance of this loop during MS onset provides further insights into how pathogenic B cells survive peripheral tolerance checkpoints to mediate disease activity in MS.

References

Mar 1, 1983·Annals of Neurology·C M PoserW W Tourtellotte
Oct 4, 1996·Science·I Shachar, R A Flavell
Dec 12, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·D AllmanR R Hardy
Feb 28, 2002·Proceedings of the National Academy of Sciences of the United States of America·Didi MatzaIdit Shachar
Sep 11, 2002·FEBS Letters·Sigrid HatseDominique Schols
Jan 23, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Claudia M DenkingerThomas G Forsthuber
Jun 5, 2003·The Journal of Experimental Medicine·Lin LengRichard Bucala
Sep 23, 2003·Nature Reviews. Immunology·Thierry Calandra, Thierry Roger
Feb 7, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Kamel BenlaghaAlbert Bendelac
Aug 10, 2004·Nature Immunology·Christopher D C AllenJason G Cyster
Nov 3, 2004·The Journal of Experimental Medicine·Yuchun NieYong-Rui Zou
Feb 15, 2008·The New England Journal of Medicine·Stephen L HauserUNKNOWN HERMES Trial Group
Jul 16, 2009·BMC Cancer·Eva VerjansJürgen Bernhagen
Aug 12, 2009·FEBS Letters·Verena SchwartzJürgen Bernhagen
Aug 24, 2010·Immunological Reviews·Yuval YarkoniJohn C Cambier
Mar 10, 2011·Annals of Neurology·Chris H PolmanJerry S Wolinsky
Jan 24, 2012·Lancet Neurology·David H MillerOlga Ciccarelli
Apr 3, 2012·The Journal of Clinical Investigation·Alyssa Nylander, David A Hafler
May 17, 2013·The Journal of Clinical Investigation·Tuure KinnunenEric Meffre
Jun 26, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Gina Mavrikis CoxCaroline C Whitacre
Apr 25, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Christina KlasenOmar El Bounkari
Jul 24, 2014·Journal of Neurology, Neurosurgery, and Psychiatry·Tessel F RuniaRogier Q Hintzen
Jul 15, 2015·The Journal of Immunology : Official Journal of the American Association of Immunologists·Susann HüttlBernd Schröder
Jul 16, 2015·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Emiel P C van der VorstChristian Weber
May 28, 2017·The Journal of Immunology : Official Journal of the American Association of Immunologists·Janna SchneppenheimBernd Schröder
Sep 15, 2017·The Journal of Immunology : Official Journal of the American Association of Immunologists·Lihi RadomirIdit Shachar
Oct 13, 2017·European Journal of Immunology·Andrea CossarizzaJakob Zimmermann
Mar 16, 2018·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Corinna SchmitzJürgen Bernhagen

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Citations

Jul 10, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Liza RijversMarvin M van Luijn
Jun 12, 2020·Der Nervenarzt·Jonas GrafHans-Peter Hartung
Dec 17, 2020·Frontiers in Immunology·Jordan T Noe, Robert A Mitchell
Jun 11, 2021·Scientific Reports·Malou JanssenMarvin M van Luijn
Sep 5, 2021·Proceedings of the National Academy of Sciences of the United States of America·Maike HartlehnertGerd Meyer Zu Horste

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Methods Mentioned

BETA
FACS
ELISA
flow cytometry
Assay
PCR

Software Mentioned

Graphpad Prism
FACSDiva
GraphPad

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