Gut homeostasis and regulatory T cell induction depend on molecular chaperone gp96 in CD11c+ cells

Scientific Reports
Yunpeng HuaBei Liu

Abstract

The intestinal immunity and tolerance are orchestrated by both the innate and the adaptive immune system. Intestinal professional antigen presenting cells (pAPCs) recognize and respond to the gut microbiota through multiple pattern-recognition receptors, including TLRs and NLRs. How gut pAPCs maintain mucosal homeostasis remains incompletely understood. Heat shock protein gp96, also known as grp94, is an essential immune chaperone for TLRs. However, the role of gp96 in regulating CD11c+ APCs in the gut immunity and tolerance is unknown. By a genetic strategy, we report here that selective deletion of gp96 from CD11c+ cells in mice results in alteration of dendritic cell and T cell subsets in the gut as well as loss of antigen-specific regulatory T cell induction in the mesenteric lymph nodes. Strikingly, these conditional gp96-null mice developed spontaneous colitis, had increased levels of systemic and fecal IgA, and were highly susceptible to chemical-induced colitis. Our findings for the first time demonstrate that gp96 is essential for CD11c+ cells to induce regulatory T cells and maintain gut homeostasis, illustrating the importance of protein immune chaperone in safeguarding against immune pathology.

References

May 1, 1986·Proceedings of the National Academy of Sciences of the United States of America·P K SrivastavaL J Old
Aug 1, 1981·Proceedings of the National Academy of Sciences of the United States of America·A S LeeD Scharff
Mar 26, 2002·Nature Reviews. Immunology·Carl G FigdorGosse J Adema
Mar 5, 2003·Annual Review of Immunology·Ralph M SteinmanMichel C Nussenzweig
Apr 14, 2005·American Journal of Physiology. Gastrointestinal and Liver Physiology·Masayuki FukataMaria T Abreu
Sep 29, 2006·World Journal of Gastroenterology : WJG·Ilaria PelusoGiovanni Monteleone
Jun 27, 2007·The Journal of Experimental Medicine·Michele L CatonBoris Reizis
Jul 11, 2007·The Journal of Experimental Medicine·Cheng-Ming SunYasmine Belkaid
Nov 17, 2007·The Journal of Clinical Investigation·Matam Vijay-KumarAndrew T Gewirtz
Aug 22, 2008·Nature·Koji AtarashiKiyoshi Takeda
Nov 6, 2009·Mucosal Immunology·E C LavelleE M Creagh
Feb 4, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jessica A MelilloChristian Schindler
Mar 3, 2010·Immunological Reviews·Kang Liu, Michel C Nussenzweig
Mar 31, 2010·The Journal of Experimental Medicine·Brian T EdelsonKenneth M Murphy
Aug 4, 2010·The Journal of Experimental Medicine·Mark Asquith, Fiona Powrie
Jan 12, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Rosalie MolenaarReina E Mebius
Apr 15, 2011·Immunological Reviews·Howard L WeinerHenry Wu
Jul 21, 2011·Journal of Leukocyte Biology·Maria Rescigno
Jan 11, 2012·Immunology and Cell Biology·Sioh-Yang TanWolfgang Weninger
Feb 10, 2012·Mucosal Immunology·O Pabst, A M Mowat
Jan 1, 2011·Frontiers in Immunology·Darren Thomas Ruane, Ed C Lavelle
Sep 11, 2012·International Immunology·Hisako Kayama, Kiyoshi Takeda
Apr 11, 2013·Proceedings of the National Academy of Sciences of the United States of America·Bei LiuZihai Li
Jun 19, 2013·Autoimmunity Reviews·Alessandra GeremiaAntonio Di Sabatino
Jul 9, 2013·Current Opinion in Immunology·Deniz Erturk-Hasdemir, Dennis L Kasper
Aug 22, 2013·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Jennifer L Owen, Mansour Mohamadzadeh

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Methods Mentioned

BETA
flow cytometry
ELISA
FACS
Protein Assay
light microscopy

Software Mentioned

FlowJo
Prism

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