exposome: an intriguing relationship between the skin … · inserm, paris cnrs, new delhi...
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INSERM, ParisCNRS, New Delhi
Exposome: An Intriguing Relationship Between the Skin and the Environment
Srini Kaveri
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Thanks
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Our Collaborators Razzaque Ahmed
(Harvard, USA)Philippe Paquet
(Liège, Belgium)Hans-Peter Hartung
(Dusseldorf, Germany)V Nagaraja/KN Balaji/DN Rao
(MCB, Biochem, IISc, India)Vir Singh Negi
(Pondicherry, India)K Ghosh
(Mumbai, India)Moses Rodriguez
(Rochester, MN)
T Vassilev / A Pashov(Sophia, Bulgaria)
S Miescher / F Kassermannvon Gunten S, Simon HU
(Bern, Swiss)
Olivier Hermine (Paris)
Eric Oksenhendler (Paris)Denis Glotz (Paris)Bernard Weill (Paris)
Marianne Debré (Paris)Yves Lévy (Créteil)Luc Mouthon (Paris)
Tarek Sharshar (Garches)
Charles Pierrot-Deseilligny/Francis Bolgert (Pitie-Salpetriere)
Laurent Magy/Jean-Michel Vallat (Limoges)
Sonia Berrih-Aknin (Clamart)André Herbelin (Paris)Olivier Benveniste (Pitie-Salpetriere)
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Immune ResponseBNB
fM
Endothelial Cells
NO
MMPs
TNFa
Clearance of Pathogens
TTTCR
MHCCo-stimulatory
Molecules
MMf
ICAMVCAMMMPs
CHEMOKINES
Adhesion Molecules
2
IL4IL6
B
Antibodies
TT
TT
C3d
C activationMAC formation
CR1
CR2
fM
Mf
Antigen
Infection?
Antibodies
DAMP/PAMP
T
Th1 Th2 Th17
T
Pro-inflammatorycytokines
Treg
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Immune Response to Non-Infectious agents
Co-stimulatoryMolecules
M
IL4IL6
BNB
Endothelial Cells
Clearance of Pathogens
f
NO
MMPs
TNFa
TTTCR
Macrophage
ICAMVCAMMMPs
CHEMOKINES
Adhesion Molecules
B
TT
TT
C3d
C activationMAC formation
CR1
CR2
fM
Mf
Antigen
Antibodies
M
MHC
2 Antibodies
T
Th1 Th2 Th17
T
Pro-inflammatorycytokines
TregX
XX
X
XX
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Immune Response to Non-Infectious agents
Co-stimulatoryMolecules
M
IL4IL6
BNB
Endothelial Cells
Clearance of Pathogens
f
NO
MMPs
TNFa
TTTCR
Macrophage
ICAMVCAMMMPs
CHEMOKINES
Adhesion Molecules
B
TT
TT
C3d
C activationMAC formation
CR1
CR2
fM
Mf
Antigen
Antibodies
M
MHC
2 Antibodies
T
Th1 Th2 Th17
T
Pro-inflammatorycytokines
Treg
Non-Infectious
agents
PollutantsAllergensSelf-Molecules
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Globe in night with lights on developed countries
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Globe in night with lights on developed countries
Geoepidemiology of immune disorders
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Pattern of Diseases Over the Past Sixty Years
JF Bach, N Eng J Med 2002
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Allergy
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Autoimmune conditions affecting the Skin
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What Happened?
What did we do to our nice little world?
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Diseases/Tissue
Homeostasis
CellularandMolecularInteractions
Environment
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Environment: A major Factor in the Emergence of Cancer
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Environment
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Our Environment
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Environment
+ClimateChange
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How do we go about ?
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How do we go about ?
Christopher Wild
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Exposome
The totality of both internal and external environmental exposures received by an individual during the entire course of life
ProteomicsTranscriptomicsMetabolomics
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Measuring the exposome
Why measure the exposome?
Why measure the skin exposome?
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Why measure the exposome?Most of a person’s increased risk of diseases is the result of environmental
rather than genetic factors
It is important to establish:the causes of diseases and to develop preventive strategies
Identify:Personal exposome for individually targeted ‘tailor-made’ health choices
And, Provide ‘feed-back’ for public health and treatment policies
modulation of specific biological pathways
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(i) skin as the first and most important barrier organ that is subject to lifelong exposure to a large variety of environmental factors,
(ii) manifestations of skin traits is significantly modulated by various internal (genetical and non-genetical) factors
and therefore
(i) research on the skin exposome may be viewed as paradigmatic and contribute to a better understanding of other organs as well
Why measure the skin exposome?
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Measuring the exposome
Wild, Int J Epidemiol, 2014
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Measuring the exposome
Wild, Int J Epidemiol, 2014
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Measuring the Exposome(Exposome-Wide Association Studies)
Molecular Basis of Physiology(and of Pathology)
Genome(DNA)
Transcriptome(RNA)
Proteome(Proteins)
Metabolome(Small Molecules)
G R P M
Interactome
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Measuring the Exposome(Exposome-Wide Association Studies)
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Measuring the Exposome(Exposome-Wide Association Studies)
Interactome
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Skin Aging Exposome
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Skin Aging Exposome
Krutmann, et al, 2016. Journal of Dermatological Science
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1. General measures• Avoid smoking.• Avoid artificial UV exposures (indoor tanning).• Avoid intentional UV exposure for cosmetic purposes. When outdoors, seek shade whenever
possible. Use protective clothing in addition to skin photoprotective care.• Maintain a healthy life-style, with a diet rich in fruits and vegetables, limited alcohol intake, and
enough sleep.2. Recommendations for daily skin care regimen
A/ In the morning:
•Avoid over washing the skin as it may damage the natural skin barrier function. Use a gentlecleanser, avoid soap.•Use cosmetic products to improve skin barrier function and use cosmetics with topicalantioxidants to reduce harmful effects of ozone and IRA on skin ageing.•Use photo protective measures: broad spectrum UVA-UVB sunscreen to block UV radiation andto prevent photo reactive compounds to being produced under UV exposure.•For darker skinned individuals consider adapted sunscreen to protect the skin from shorterwavelength visible light in addition to well-balanced UVA / UVB protection.
B/ In the evening:•Use rinse-off products (gels, shampoos) to clean off pollution on the skin surface and to reduceparticle load.•Use cosmetic products to improve skin barrier function and to repair aging signs.
General Recommendations
Krutmann, et al, 2016. Journal of Dermatological Science
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Exposome and tissue homeostasis
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Back Up Slides
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