IL-33, an Endogenous Danger Signal from the IL-1 Family Jean-Philippe Girard, Director, Institute of Pharmacology and Structural Biology, CNRS-University of Toulouse, France
Beginners Guide to TikTok for Search - Rachel Pearson - We are Tilt __ Bright...
IL-33, an Endogenous Danger Signal from the IL-1 Family Jean-Philippe Girard, Director, Institute of Pharmacology and Structural Biology, CNRS-University of Toulouse, France
1. IL-33, an endogenous danger signal from the IL-1 family
Jean-Philippe GIRARD, PhD
Director, Institute of Pharmacology and Structural Biology
(IPBS-CNRS, a 260-people Institute from CNRS and Université de Toulouse)
Jean-Philippe GIRARD 8th Cytokines & Inflammation Conference San Diego, CA January 28-29, 2010
2. Discovery of NF-HEV, a nuclear factor from high
endothelial venules (Baekkevold …and Girard, Am J Path, 2003, 163:69-79)
High endothelial venules (HEV): specialized blood vessels for lymphocyte migration
(Girard and Springer, Immunol. Today, 1995; Girard and Springer, Immunity, 1995; Lacorre ...and Girard, Blood, 2004)
HUMAN TONSIL HEV A MECA-79 DAPI MECA-79
lumen lumen
B NF-HEV DAPI NF-HEV
SULFATED EPITOPE MECA-79
lumen lumen
Blood
C MERGE DAPI MERGE
Lymphocytes, dendritic cells, ..
lumen lumen
Jean-Philippe GIRARD 8th Cytokines & Inflammation Conference San Diego, CA January 28-29, 2010
3. NF-HEV is identical to interleukin-33 (IL-33), an IL-1-
like cytokine that signals via ST2/IL-1R4
(Schmitz…and Kastelein, Immunity, 2005; Chackerian et al., J Immunol 2007)
NF-HEV/IL-33
(30.7 kDa)
IL-33 IL-1
IL-1a
IL-1RAcP
IL-1RAcP
(30.6 kDa)
ST2 IL-1R
IL-1b
(30.7 kDa)
IL-33 Th2 cell MyD88 MyD88
Mast cell IRAK IRAK
TRAF6 TRAF6
ST2
mRNA
NF-kB MAP kinases
IL-4
IL-5 IL-13
Jean-Philippe GIRARD 8th Cytokines & Inflammation Conference San Diego, CA January 28-29, 2010
4. IL-33 activates various immune cell types
(from D. Smith, Clinical & Experimental Allergy, 2009, 1-9)
Jean-Philippe GIRARD 8th Cytokines & Inflammation Conference San Diego, CA January 28-29, 2010
5. IL-33 has been linked to important human diseases
Allergic diseases such as asthma, atopic dermatitis and
allergic rhinitis (Schmitz et al. Immunity 2005; Gudbjartsson
et al., Nat Genet 2009; Pushparaj et al., PNAS 2009; …) IL-33
IL-1RAcP
Rheumatoid arthritis (Carriere et al. PNAS 2007; Xu et al., ST2
PNAS 2008; Palmer et al., Arthritis Rheum 2009; …)
Cardiovascular diseases (atherosclerosis, myocardial
MyD88
infarction, heart failure; Sanada et al., J Clin Invest 2007;
IRAK
Miller et al., J Exp Med 2008; …)
TRAF6
Alzheimer’s disease (Chapuis et al., Mol Psychiatry 2009)
Jean-Philippe GIRARD 8th Cytokines & Inflammation Conference San Diego, CA January 28-29, 2010
6. IL-33 is a chromatin-associated IL-1-like cytokine
(Carriere, …and Girard, PNAS, 2007, 104:282-287)
IL-33
HEV NF-HEV / IL-33
DAPI IL-33
Jean-Philippe GIRARD 8th Cytokines & Inflammation Conference San Diego, CA January 28-29, 2010
7. Molecular mimicry between IL-33 and Kaposi’s sarcoma
herpesvirus LANA for attachment to chromatin
(Roussel …and Girard, EMBO Reports, 2008, 9:1006-1012)
KSHV episome
LANA
CB
M
CB
M
Barbera …and Kaye, Science 2006
Jean-Philippe GIRARD 8th Cytokines & Inflammation Conference San Diego, CA January 28-29, 2010
8. IL-33 is constitutively expressed in the nucleus
of endothelial cells from normal human tissues
(Moussion*, Ortega* and Girard, PLoS ONE, 2008, 3(10):e3331)
Jean-Philippe GIRARD 8th Cytokines & Inflammation Conference San Diego, CA January 28-29, 2010
9. ATTENTION!
The entire presentation is available to registered
attendees only!
To view the rest of this exciting presentation and many
more!
Please Register for the
8th Annual Cytokines & Inflammation Conference
at
www.gtcbio.com
If you are already registered, please contact
GTCbio for the full version.
