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Immunity activation in the skin

A) Our group studies innate immunity activation in the skin, which is the first barrier protecting us from our environment. We focus our research on the role of a new set of danger sensors, called NLR, that represent intracellular equivalents of Toll like receptors (TLR) and activate pro-inflamatory cytokines such as IL-1beta. Our recent work has provided a better understanding of T cell priming in contact hypersensitivity (CHS), a delayed type hypersensitivity that occurs when sensitizing chemicals penetrate the skin surface. Using mouse models and in vitro assays, we demonstrated that contact sensitizer activates NLRs, and that this activation is essential for T cell priming and CHS. We are now studying the role of NLRs as master switches between tolerance and sensitization. In addition, we are studying if similar mechanisms may be involved in the modulation of UV induced carcinogenesis and psoriasis development.

B) Dysfunction in the signaling pathway of the TNF family ligand Ectodysplasin A (EDA) causes hypohidrotic ectodermal dysplasia (HED), a severe disease characterized by the lack of development of skin appendages such as hair, teeth and sweat glands. We have designed and produced a recombinant form of EDA that reverts HED in mice and dogs. We are now contributing to the preclinical (safety) studies that may one day render human therapy possible (Orphan drug designation at the FDA/EMEA).

Group's publications

Classifying ectodermal dysplasias: Incorporating the molecular basis and pathways (Workshop II).
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
2009 vol. 149A(9) pp. 2062-2067
WRIGHT JT, MORRIS C, CLEMENTS SE, D'SOUZA R, GAIDE O, MIKKOLA M, ZONANA J

Gene therapy and protein therapy of ectodermal dysplasias: a perspective.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
2009 vol. 149A(9) pp. 2042-2044
GAIDE O

Neonatal Treatment With Recombinant Ectodysplasin Prevents Respiratory Disease in Dogs With X-Linked Ectodermal Dysplasia
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
2009 vol. 149A(9) pp. 2045-2049
MAULDIN EA, GAIDE O, SCHNEIDER P, CASAL ML

Biological activity of ectodysplasin A is conditioned by its collagen and heparan sulfate proteoglycan-binding domains.
JOURNAL OF BIOLOGICAL CHEMISTRY
2009 vol. 284(40) pp. 27567-27576
SWEE LK, INGOLD-SALAMIN K, TARDIVEL A, WILLEN L, GAIDE O, FAVRE M, DEMOTZ S, MIKKOLA M, SCHNEIDER P

2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) poisoning in Victor Yushchenko: identification and measurement of TCDD metabolites.
LANCET
2009 vol. 374(9696) pp. 1179-1185
SORG O, ZENNEGG M, SCHMID P, FEDOSYUK R, VALIKHNOVSKYI R, GAIDE O, KNIASEVYCH V, SAURAT JH

Resistance to FasL and tumor necrosis factor-related apoptosis-inducing ligand-mediated apoptosis in Sezary syndrome T-cells associated with impaired death receptor and FLICE-inhibitory protein expres sion.
BLOOD
2008 vol. 111(9) pp. 4780-4787
CONTASSOT E, KERL K, ROQUES S, SHANE R, GAIDE O, DUPUIS M, ROOK AH, FRENCH LE

Danger signaling through the inflammasome acts as a master switch between tolerance and sensitization.
JOURNAL OF IMMUNOLOGY
2008 vol. 180(9) pp. 5826-5832
WATANABE H, GEHRKE S, CONTASSOT E, ROQUES S, TSCHOPP J, FRIEDMANN PS, FRENCH LE, GAIDE O

Community-acquired methicillin-resistant Staphylococcus aureus infections in two scuba divers returning from the Philippines.
JOURNAL OF TRAVEL MEDICINE : OFFICIAL PUBLICATION OF THE INTERNATIONAL SOCIETY OF TRAVEL MEDICINE AND THE ASIA PACIFIC TRAVEL HEALTH ASSOCIATION
2008 vol. 15(5) pp. 378-381
BOCHET M, FRANCOIS P, LONGTIN Y, GAIDE O, RENZI G, HARBARTH S

The proteolytic activity of the paracaspase MALT1 is key in T cell activation.
NATURE IMMUNOLOGY
2008 vol. 9(3) pp. 272-281
REBEAUD F AND AL.

Significant correction of disease after postnatal administration of recombinant ectodysplasin a in canine x-linked ectodermal dysplasia
AMERICAN JOURNAL OF HUMAN GENETICS
2007 vol. 81 pp. 1050-1056
CASAL, ML, LEWIS, JR, MAULDIN, EA, TARDIVEL, A, INGOLD, K, FAVRE, M, PARADIES, F, DEMOTZ, S, GAIDE, O, SCHNEIDER, P

Exclusively benign dermoscopic pattern in a patient with acral melanoma
ARCHIVES OF DERMATOLOGY
2007 vol. 143(9) pp. 1213-1215
BRAUN RP, GAIDE O, SKARIA AM, KOPF AW, SAURAT JH, MARGHOOB AA

Can automated dermoscopy image analysis instruments provide added benefit for the dermatologist? A study comparing the results of three systems
BRITISH JOURNAL OF DERMATOLOGY
2007 vol. 157 pp. 926-933
PERRINAUD, A, GAIDE, O, FRENCH, LE, SAURAT, JH, MARGHOOB, AA, BRAUN, RP

The significance of multiple blue-grey dots (granularity) for the dermoscopic diagnosis of melanoma
BRITISH JOURNAL OF DERMATOLOGY
2007 vol. 157 pp. 907-913
BRAUN, RP, GAIDE, O, OLIVIERO, M, KOPF, AW, FRENCH, LE, SAURAT, JH, RABINOVITZ, HS

Death receptors and apoptosis
DERMATOLOGIC CLINICS
2007 vol. 25 pp. 487-501
CONTASSOT, E, GAIDE, O, FRENCH, LE

Bcl10 controls TCR- and Fc gamma R-induced actin polymerization
JOURNAL OF IMMUNOLOGY
2007 vol. 178 pp. 4373-4384
RUEDA, D, GAIDE, O, HO, LZ, LEWKOWICZ, E, NIEDERGANG, F, HAILFINGER, S, REBEAUD, F, GUZZARDI, M, CONNE, B, THELEN, M, DELON, J, FERCH, U, MAK, TW, RULAND, J, SCHWALLER, J, THOME, M

Activation of the IL-1 beta-Processing inflammasome is involved in contact hypersensitivity
JOURNAL OF INVESTIGATIVE DERMATOLOGY
2007 vol. 127 pp. 1956-1963
WATANABE, H, GAIDE, O, PETRILLI, V, MARTINON, F, CONTASSOT, E, ROQUES, S, KUMMER, JA, TSCHOPP, J, FRENCH, LE

Diagnosis and management of nail pigmentations
JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
2007 vol. 56 pp. 835-847
BRAUN, RP, BARAN, R, LE GAL, FA, DALLE, S, RONGER, S, PANDOLFI, R, GAIDE, O, FRENCH, LE, LAUGIER, P, SAURAT, JH, MARGHOOB, AA, THOMAS, L

NALP inflammasomes: a central role in innate immunity
SEMINARS IN IMMUNOLOGY
2007 vol. 29(3) pp. 213-229
MARTINON F, GAIDE O, PÉTRILLI V, MAYOR A, TSCHOPP J

Interactions of tumor necrosis factor (TNF) and TNF receptor family members in the mouse and human
JOURNAL OF BIOLOGICAL CHEMISTRY
2006 vol. 281(20) pp. 13964-13971
BOSSEN C, INGOLD K, TARDIVEL A, BODMER JL, GAIDE O, HERTIG S, AMBROSE C, TSCHOPP J, SCHNEIDER P

Ectodysplasin A1 promotes placodal cell fate during early morphogenesis of ectodermal appendages.
DEVELOPMENT
2004 vol. 131(20) pp. 4907-4919
MUSTONEN T, ILMONEN M, PUMMILA M, KANGAS AT, LAURIKKALA J, JAATINEN R, PISPA J, GAIDE O, SCHNEIDER P, THESLEFF I, MIKKOLA ML

Vitamin A exerts a photoprotective action in skin by absorbing ultraviolet B radiation
JOURNAL OF INVESTIGATIVE DERMATOLOGY
2003 vol. 121 pp. 1163-1167
ANTILLE C, TRAN CHRISTIAN, SORG O, CARRAUX P, DIDIERJEAN L, SAURAT JH

Decreased oxidative state in non-lesional skin of atopic dermatitis
DERMATOLOGY--
2002 vol. 204 pp. 69-71
ANTILLE C, SORG O, LUBBE J, SAURAT JH

Staphylococcal Colonization in Atopic Dermatitis Treatment with Topical Tacrolimus (Fk506)
JOURNAL OF INVESTIGATIVE DERMATOLOGY
2001 vol. 116 pp. 480-481
POURNARAS CC, LUBBE J, SAURAT JH

Decrease in epidermal CD44 expression as a potential mechanism for abnormal hyaluronate accumulation in superficial dermis in lichen sclerosus et atrophicus
JOURNAL OF INVESTIGATIVE DERMATOLOGY
2000 vol. 115(6) pp. 1054-1058
KAYA GURKAN, AUGSBURGER ERIC, STAMENKOVIC I, SAURAT JEAN-HILAIRE

The CCR4 and CAF1 proteins of the CCR4-NOT complex are physically and functionally separated from NOT2, NOT4, and NOT5.
MOLECULAR AND CELLULAR BIOLOGY : MCB
1999 vol. 19 pp. 6642-6651
BAI Y, SALVADORE C., CHIANG Y.-C., COLLART MARTINE, LIU H.-Y., DENIS C.L.

Research's domains




DATABASE-RESEARCH	GROUP OF CLINICAL BIOLOGY RESEARCH

Olivier GAIDE	Head of group CV	Research subject	Members of the group


	Links about the group Dr. O. GAIDE CMU / Dpt PATIM Rue Michel Servet 1 1211 Genève 4 Suisse Olivier.gaide@unige.ch Tel.: 022 379 58 08 Fax: 022 379 58 02 Comments Pages updated the 17.11.2015		Reseach's subject \| Group's publications \| Research's domains Immunity activation in the skin A) Our group studies innate immunity activation in the skin, which is the first barrier protecting us from our environment. We focus our research on the role of a new set of danger sensors, called NLR, that represent intracellular equivalents of Toll like receptors (TLR) and activate pro-inflamatory cytokines such as IL-1beta. Our recent work has provided a better understanding of T cell priming in contact hypersensitivity (CHS), a delayed type hypersensitivity that occurs when sensitizing chemicals penetrate the skin surface. Using mouse models and in vitro assays, we demonstrated that contact sensitizer activates NLRs, and that this activation is essential for T cell priming and CHS. We are now studying the role of NLRs as master switches between tolerance and sensitization. In addition, we are studying if similar mechanisms may be involved in the modulation of UV induced carcinogenesis and psoriasis development. B) Dysfunction in the signaling pathway of the TNF family ligand Ectodysplasin A (EDA) causes hypohidrotic ectodermal dysplasia (HED), a severe disease characterized by the lack of development of skin appendages such as hair, teeth and sweat glands. We have designed and produced a recombinant form of EDA that reverts HED in mice and dogs. We are now contributing to the preclinical (safety) studies that may one day render human therapy possible (Orphan drug designation at the FDA/EMEA). Group's publications Classifying ectodermal dysplasias: Incorporating the molecular basis and pathways (Workshop II). AMERICAN JOURNAL OF MEDICAL GENETICS PART A 2009 vol. 149A(9) pp. 2062-2067 WRIGHT JT, MORRIS C, CLEMENTS SE, D'SOUZA R, GAIDE O, MIKKOLA M, ZONANA J Gene therapy and protein therapy of ectodermal dysplasias: a perspective. AMERICAN JOURNAL OF MEDICAL GENETICS PART A 2009 vol. 149A(9) pp. 2042-2044 GAIDE O Neonatal Treatment With Recombinant Ectodysplasin Prevents Respiratory Disease in Dogs With X-Linked Ectodermal Dysplasia AMERICAN JOURNAL OF MEDICAL GENETICS PART A 2009 vol. 149A(9) pp. 2045-2049 MAULDIN EA, GAIDE O, SCHNEIDER P, CASAL ML Biological activity of ectodysplasin A is conditioned by its collagen and heparan sulfate proteoglycan-binding domains. JOURNAL OF BIOLOGICAL CHEMISTRY 2009 vol. 284(40) pp. 27567-27576 SWEE LK, INGOLD-SALAMIN K, TARDIVEL A, WILLEN L, GAIDE O, FAVRE M, DEMOTZ S, MIKKOLA M, SCHNEIDER P 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) poisoning in Victor Yushchenko: identification and measurement of TCDD metabolites. LANCET 2009 vol. 374(9696) pp. 1179-1185 SORG O, ZENNEGG M, SCHMID P, FEDOSYUK R, VALIKHNOVSKYI R, GAIDE O, KNIASEVYCH V, SAURAT JH Resistance to FasL and tumor necrosis factor-related apoptosis-inducing ligand-mediated apoptosis in Sezary syndrome T-cells associated with impaired death receptor and FLICE-inhibitory protein expres sion. BLOOD 2008 vol. 111(9) pp. 4780-4787 CONTASSOT E, KERL K, ROQUES S, SHANE R, GAIDE O, DUPUIS M, ROOK AH, FRENCH LE Danger signaling through the inflammasome acts as a master switch between tolerance and sensitization. JOURNAL OF IMMUNOLOGY 2008 vol. 180(9) pp. 5826-5832 WATANABE H, GEHRKE S, CONTASSOT E, ROQUES S, TSCHOPP J, FRIEDMANN PS, FRENCH LE, GAIDE O Community-acquired methicillin-resistant Staphylococcus aureus infections in two scuba divers returning from the Philippines. JOURNAL OF TRAVEL MEDICINE : OFFICIAL PUBLICATION OF THE INTERNATIONAL SOCIETY OF TRAVEL MEDICINE AND THE ASIA PACIFIC TRAVEL HEALTH ASSOCIATION 2008 vol. 15(5) pp. 378-381 BOCHET M, FRANCOIS P, LONGTIN Y, GAIDE O, RENZI G, HARBARTH S The proteolytic activity of the paracaspase MALT1 is key in T cell activation. NATURE IMMUNOLOGY 2008 vol. 9(3) pp. 272-281 REBEAUD F AND AL. Significant correction of disease after postnatal administration of recombinant ectodysplasin a in canine x-linked ectodermal dysplasia AMERICAN JOURNAL OF HUMAN GENETICS 2007 vol. 81 pp. 1050-1056 CASAL, ML, LEWIS, JR, MAULDIN, EA, TARDIVEL, A, INGOLD, K, FAVRE, M, PARADIES, F, DEMOTZ, S, GAIDE, O, SCHNEIDER, P Exclusively benign dermoscopic pattern in a patient with acral melanoma ARCHIVES OF DERMATOLOGY 2007 vol. 143(9) pp. 1213-1215 BRAUN RP, GAIDE O, SKARIA AM, KOPF AW, SAURAT JH, MARGHOOB AA Can automated dermoscopy image analysis instruments provide added benefit for the dermatologist? A study comparing the results of three systems BRITISH JOURNAL OF DERMATOLOGY 2007 vol. 157 pp. 926-933 PERRINAUD, A, GAIDE, O, FRENCH, LE, SAURAT, JH, MARGHOOB, AA, BRAUN, RP The significance of multiple blue-grey dots (granularity) for the dermoscopic diagnosis of melanoma BRITISH JOURNAL OF DERMATOLOGY 2007 vol. 157 pp. 907-913 BRAUN, RP, GAIDE, O, OLIVIERO, M, KOPF, AW, FRENCH, LE, SAURAT, JH, RABINOVITZ, HS Death receptors and apoptosis DERMATOLOGIC CLINICS 2007 vol. 25 pp. 487-501 CONTASSOT, E, GAIDE, O, FRENCH, LE Bcl10 controls TCR- and Fc gamma R-induced actin polymerization JOURNAL OF IMMUNOLOGY 2007 vol. 178 pp. 4373-4384 RUEDA, D, GAIDE, O, HO, LZ, LEWKOWICZ, E, NIEDERGANG, F, HAILFINGER, S, REBEAUD, F, GUZZARDI, M, CONNE, B, THELEN, M, DELON, J, FERCH, U, MAK, TW, RULAND, J, SCHWALLER, J, THOME, M Activation of the IL-1 beta-Processing inflammasome is involved in contact hypersensitivity JOURNAL OF INVESTIGATIVE DERMATOLOGY 2007 vol. 127 pp. 1956-1963 WATANABE, H, GAIDE, O, PETRILLI, V, MARTINON, F, CONTASSOT, E, ROQUES, S, KUMMER, JA, TSCHOPP, J, FRENCH, LE Diagnosis and management of nail pigmentations JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY 2007 vol. 56 pp. 835-847 BRAUN, RP, BARAN, R, LE GAL, FA, DALLE, S, RONGER, S, PANDOLFI, R, GAIDE, O, FRENCH, LE, LAUGIER, P, SAURAT, JH, MARGHOOB, AA, THOMAS, L NALP inflammasomes: a central role in innate immunity SEMINARS IN IMMUNOLOGY 2007 vol. 29(3) pp. 213-229 MARTINON F, GAIDE O, PÉTRILLI V, MAYOR A, TSCHOPP J Interactions of tumor necrosis factor (TNF) and TNF receptor family members in the mouse and human JOURNAL OF BIOLOGICAL CHEMISTRY 2006 vol. 281(20) pp. 13964-13971 BOSSEN C, INGOLD K, TARDIVEL A, BODMER JL, GAIDE O, HERTIG S, AMBROSE C, TSCHOPP J, SCHNEIDER P Ectodysplasin A1 promotes placodal cell fate during early morphogenesis of ectodermal appendages. DEVELOPMENT 2004 vol. 131(20) pp. 4907-4919 MUSTONEN T, ILMONEN M, PUMMILA M, KANGAS AT, LAURIKKALA J, JAATINEN R, PISPA J, GAIDE O, SCHNEIDER P, THESLEFF I, MIKKOLA ML Vitamin A exerts a photoprotective action in skin by absorbing ultraviolet B radiation JOURNAL OF INVESTIGATIVE DERMATOLOGY 2003 vol. 121 pp. 1163-1167 ANTILLE C, TRAN CHRISTIAN, SORG O, CARRAUX P, DIDIERJEAN L, SAURAT JH Decreased oxidative state in non-lesional skin of atopic dermatitis DERMATOLOGY-- 2002 vol. 204 pp. 69-71 ANTILLE C, SORG O, LUBBE J, SAURAT JH Staphylococcal Colonization in Atopic Dermatitis Treatment with Topical Tacrolimus (Fk506) JOURNAL OF INVESTIGATIVE DERMATOLOGY 2001 vol. 116 pp. 480-481 POURNARAS CC, LUBBE J, SAURAT JH Decrease in epidermal CD44 expression as a potential mechanism for abnormal hyaluronate accumulation in superficial dermis in lichen sclerosus et atrophicus JOURNAL OF INVESTIGATIVE DERMATOLOGY 2000 vol. 115(6) pp. 1054-1058 KAYA GURKAN, AUGSBURGER ERIC, STAMENKOVIC I, SAURAT JEAN-HILAIRE The CCR4 and CAF1 proteins of the CCR4-NOT complex are physically and functionally separated from NOT2, NOT4, and NOT5. MOLECULAR AND CELLULAR BIOLOGY : MCB 1999 vol. 19 pp. 6642-6651 BAI Y, SALVADORE C., CHIANG Y.-C., COLLART MARTINE, LIU H.-Y., DENIS C.L. Research's domains