Myeloid cells, BAFF, and IFN-gamma establish an inflammatory loop that exacerbates autoimmunity in Lyn-deficient mice.

The Journal of Experimental Medicine
Patrizia ScapiniClifford A Lowell

Abstract

Autoimmunity is traditionally attributed to altered lymphoid cell selection and/or tolerance, whereas the contribution of innate immune cells is less well understood. Autoimmunity is also associated with increased levels of B cell-activating factor of the TNF family (BAFF; also known as B lymphocyte stimulator), a cytokine that promotes survival of self-reactive B cell clones. We describe an important role for myeloid cells in autoimmune disease progression. Using Lyn-deficient mice, we show that overproduction of BAFF by hyperactive myeloid cells contributes to inflammation and autoimmunity in part by acting directly on T cells to induce the release of IFN-gamma. Genetic deletion of IFN-gamma or reduction of BAFF activity, achieved by either reducing myeloid cell hyperproduction or by treating with an anti-BAFF monoclonal antibody, reduced disease development in lyn(-/-) mice. The increased production of IFN-gamma in lyn(-/-) mice feeds back on the myeloid cells to further stimulate BAFF release. Expression of BAFF receptor on T cells was required for their full activation and IFN-gamma release. Overall, our data suggest that the reciprocal production of BAFF and IFN-gamma establishes an inflammatory loop between myeloid cells...Continue Reading

References

Feb 7, 1998·The Journal of Clinical Investigation·D BalomenosA N Theofilopoulos
Nov 21, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·B HuardL E French
Mar 22, 2002·Nature Reviews. Immunology·M J ShlomchikM J Mamula
May 29, 2002·Oncogene·Sushil G Rane, E Premkumar Reddy
Jul 3, 2002·The Journal of Experimental Medicine·Philip L CohenElizabeth A Reap
Jul 23, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Shalini Pereira, Clifford Lowell
Jun 29, 2004·Molecular Immunology·Clifford A Lowell
Jul 9, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Lai Guan NgCharles R Mackay
Sep 16, 2004·European Journal of Immunology·Qunrui YeWayne W Hancock
Jan 25, 2005·Immunity·Yuekang XuDavid M Tarlinton
Mar 26, 2005·Immunological Reviews·Susan L Kalled
Mar 31, 2005·Trends in Immunology·Giorgio BertonClifford A Lowell
Apr 15, 2005·Molecular Immunology·Lai Guan NgFabienne Mackay
Apr 22, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Andrew P R SutherlandCharles R Mackay
May 12, 2005·Current Opinion in Immunology·Pascal Schneider
Jun 14, 2005·The Journal of Clinical Investigation·Jiankun ZhuChandra Mohan
Aug 12, 2005·Current Opinion in Rheumatology·Harini Bagavant, Shu Man Fu
Aug 24, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ching-Liang Chu, Clifford A Lowell
Feb 18, 2006·The Journal of Clinical Investigation·Meera RamanujamAnne Davidson
Mar 8, 2006·The Journal of Experimental Medicine·Yoshikatsu KanekoJeffrey V Ravetch
Aug 26, 2006·Seminars in Immunology·Fabienne Mackay, Helen Leung
Feb 22, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Rachel EttingerPeter E Lipsky
Apr 17, 2007·Current Opinion in Immunology·Fabienne MackayRobert Brink
Sep 14, 2007·European Journal of Immunology·Karlee L SilverRichard J Cornall
Oct 20, 2007·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Stefanie SarantopoulosJerome Ritz
Feb 29, 2008·The New England Journal of Medicine·Anisur Rahman, David A Isenberg
May 6, 2008·Current Opinion in Immunology·Jason E Stadanlick, Michael P Cancro
Jun 14, 2008·Nature Reviews. Immunology·John A Hamilton
Jul 11, 2008·Immunological Reviews·Meera Ramanujam, Anne Davidson
Jul 11, 2008·Immunological Reviews·Koichi YanabaThomas F Tedder
Jul 22, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Masayoshi HarigaiNobuyuki Miyasaka
Sep 30, 2008·Proceedings of the National Academy of Sciences of the United States of America·Queenie Lai Kwan LamLiwei Lu
Oct 4, 2008·Proceedings of the National Academy of Sciences of the United States of America·Jean L ScholzMichael P Cancro

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Citations

Nov 28, 2012·Journal of Clinical Immunology·Gang HuangFengtian He
Sep 14, 2011·Proceedings of the National Academy of Sciences of the United States of America·Patrizia ScapiniClifford A Lowell
Aug 14, 2013·Proceedings of the National Academy of Sciences of the United States of America·Chrystelle LamagnaClifford A Lowell
Dec 10, 2002·Annual Review of Immunology·Ronald H Schwartz
Mar 16, 2011·Journal of Biomedicine & Biotechnology·Daniel PerryLaurence Morel
May 24, 2011·Cancer Research·Kaihua ZhangRoberta Faccio
Jul 19, 2012·Cell Communication and Signaling : CCS·Evan Ingley
Jan 11, 2013·Arthritis Research & Therapy·Alexis Boneparth, Anne Davidson
Jul 4, 2012·Journal of Leukocyte Biology·Samuel E VaughnJohn B Harley
Jan 15, 2014·Cytokine & Growth Factor Reviews·Maogen ChenSong Guo Zheng
Apr 27, 2012·Current Rheumatology Reports·Anne Davidson
Nov 8, 2011·European Journal of Immunology·Gitit ShahafRamit Mehr
Jun 16, 2015·American Journal of Respiratory and Critical Care Medicine·Francesca PolverinoCaroline A Owen
Sep 1, 2015·Frontiers in Immunology·Megan WoodsAnne Davidson
Nov 13, 2013·Autoimmunity·Inez RogatskyAlessandra B Pernis
Nov 20, 2013·Autoimmunity·Van Phi LuuAlbert Zlotnik
Jan 23, 2015·Frontiers in Immunology·Matthew C MorrisLiwu Li
Nov 18, 2015·American Journal of Respiratory Cell and Molecular Biology·Meenal Sinha, Clifford A Lowell
Jan 24, 2012·Veterinary Immunology and Immunopathology·Rachelle BuchananHeather L Wilson
Jan 28, 2014·Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation·Caron A JacobsonStefanie Sarantopoulos
Jan 5, 2017·British Journal of Pharmacology·Andrew P Sage, Ziad Mallat
Jul 11, 2018·The Journal of Immunology : Official Journal of the American Association of Immunologists·Young-In KimSun-Young Chang
Sep 26, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Rada EllegårdMarie Larsson
Jul 8, 2015·The Journal of Immunology : Official Journal of the American Association of Immunologists·Toshiharu AbeGeorge Hajishengallis
Nov 19, 2015·Frontiers in Immunology·Timothy A GottschalkMargaret L Hibbs
Jun 28, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Zheng LiuAnne Davidson
Sep 20, 2011·European Journal of Immunology·Andrew J GrossAnthony L DeFranco
Mar 15, 2015·The Journal of Immunology : Official Journal of the American Association of Immunologists·Robyn E MillsMichelle L Hermiston
Apr 5, 2017·Rheumatology·Olga ZharkovaLaurie S Davis
Jul 6, 2018·Frontiers in Immunology·Jincy M IssacBasel K Al-Ramadi
Apr 12, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Danielle L KrebsKenneth W Harder
Sep 16, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Emily R ElliottClifford A Lowell
Oct 25, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Maria J SmolinskaNicole J Horwood
Nov 16, 2011·Annals of the New York Academy of Sciences·Roberta Faccio
Jul 17, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Evelyn TsantikosMargaret L Hibbs
Nov 22, 2012·European Journal of Immunology·Toni GutierrezAnne B Satterthwaite
Jan 1, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Zhaolin HuaAnthony L DeFranco
Aug 30, 2016·The Journal of Clinical Investigation·Irina ProektAnthony L DeFranco
Oct 24, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Morgan E RobertsKenneth W Harder

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Methods Mentioned

BETA
ELISA
FACS
PMA
Flow cytometry
Assay
MDS
Infrared Imaging
PCR

Software Mentioned

FlowJo

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