INSERM, ParisCNRS, New Delhi

Exposome: An Intriguing Relationship Between the Skin and the Environment

Srini Kaveri

Thanks

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)

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

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

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

Globe in night with lights on developed countries

Globe in night with lights on developed countries

Geoepidemiology of immune disorders

Pattern of Diseases Over the Past Sixty Years

JF Bach, N Eng J Med 2002

Allergy

Autoimmune conditions affecting the Skin

What Happened?

What did we do to our nice little world?

Diseases/Tissue

Homeostasis

CellularandMolecularInteractions

Environment

Environment: A major Factor in the Emergence of Cancer

Environment

Our Environment

Environment

+ClimateChange

How do we go about ?

How do we go about ?

Christopher Wild

Exposome

The totality of both internal and external environmental exposures received by an individual during the entire course of life

ProteomicsTranscriptomicsMetabolomics

Measuring the exposome

Why measure the exposome?

Why measure the skin exposome?

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

(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?

Measuring the exposome

Wild, Int J Epidemiol, 2014

Measuring the exposome

Wild, Int J Epidemiol, 2014

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

Measuring the Exposome(Exposome-Wide Association Studies)

Measuring the Exposome(Exposome-Wide Association Studies)

Interactome

Skin Aging Exposome

Skin Aging Exposome

Krutmann, et al, 2016. Journal of Dermatological Science

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

Exposome and tissue homeostasis

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