Langerhans cells protect from allergic contact dermatitis in mice by tolerizing CD8(+) T cells and activating Foxp3(+) regulatory T cells.

2.50
HDL Handle:
http://hdl.handle.net/10033/240571
Title:
Langerhans cells protect from allergic contact dermatitis in mice by tolerizing CD8(+) T cells and activating Foxp3(+) regulatory T cells.
Authors:
Gomez de Agüero, Mercedes; Vocanson, Marc; Hacini-Rachinel, Fériel; Taillardet, Morgan; Sparwasser, Tim; Kissenpfennig, Adrien; Malissen, Bernard; Kaiserlian, Dominique; Dubois, Bertrand
Abstract:
Allergic contact dermatitis is the most frequent occupational disease in industrialized countries. It is caused by CD8(+) T cell-mediated contact hypersensitivity (CHS) reactions triggered at the site of contact by a variety of chemicals, also known as weak haptens, present in fragrances, dyes, metals, preservatives, and drugs. Despite the myriad of potentially allergenic substances that can penetrate the skin, sensitization is relatively rare and immune tolerance to the substance is often induced by as yet poorly understood mechanisms. Here we show, using the innocuous chemical 2,4-dinitrothiocyanobenzene (DNTB), that cutaneous immune tolerance in mice critically depends on epidermal Langerhans cells (LCs), which capture DNTB and migrate to lymph nodes for direct presentation to CD8(+) T cells. Depletion and adoptive transfer experiments revealed that LCs conferred protection from development of CHS by a mechanism involving both anergy and deletion of allergen-specific CD8(+) T cells and activation of a population of T cells identified as ICOS(+)CD4(+)Foxp3(+) Tregs. Our findings highlight the critical role of LCs in tolerance induction in mice to the prototype innocuous hapten DNTB and suggest that strategies targeting LCs might be valuable for prevention of cutaneous allergy.
Affiliation:
INSERM, U851, Lyon, France.
Citation:
Langerhans cells protect from allergic contact dermatitis in mice by tolerizing CD8(+) T cells and activating Foxp3(+) regulatory T cells. 2012, 122 (5):1700-11 J. Clin. Invest.
Journal:
The Journal of clinical investigation
Issue Date:
1-May-2012
URI:
http://hdl.handle.net/10033/240571
DOI:
10.1172/JCI59725
PubMed ID:
22523067
Type:
Article
Language:
en
ISSN:
1558-8238
Appears in Collections:
publications of the TwinCore unit Infection immunology

Full metadata record

DC FieldValueLanguage
dc.contributor.authorGomez de Agüero, Mercedesen_GB
dc.contributor.authorVocanson, Marcen_GB
dc.contributor.authorHacini-Rachinel, Férielen_GB
dc.contributor.authorTaillardet, Morganen_GB
dc.contributor.authorSparwasser, Timen_GB
dc.contributor.authorKissenpfennig, Adrienen_GB
dc.contributor.authorMalissen, Bernarden_GB
dc.contributor.authorKaiserlian, Dominiqueen_GB
dc.contributor.authorDubois, Bertranden_GB
dc.date.accessioned2012-08-30T08:49:33Z-
dc.date.available2012-08-30T08:49:33Z-
dc.date.issued2012-05-01-
dc.identifier.citationLangerhans cells protect from allergic contact dermatitis in mice by tolerizing CD8(+) T cells and activating Foxp3(+) regulatory T cells. 2012, 122 (5):1700-11 J. Clin. Invest.en_GB
dc.identifier.issn1558-8238-
dc.identifier.pmid22523067-
dc.identifier.doi10.1172/JCI59725-
dc.identifier.urihttp://hdl.handle.net/10033/240571-
dc.description.abstractAllergic contact dermatitis is the most frequent occupational disease in industrialized countries. It is caused by CD8(+) T cell-mediated contact hypersensitivity (CHS) reactions triggered at the site of contact by a variety of chemicals, also known as weak haptens, present in fragrances, dyes, metals, preservatives, and drugs. Despite the myriad of potentially allergenic substances that can penetrate the skin, sensitization is relatively rare and immune tolerance to the substance is often induced by as yet poorly understood mechanisms. Here we show, using the innocuous chemical 2,4-dinitrothiocyanobenzene (DNTB), that cutaneous immune tolerance in mice critically depends on epidermal Langerhans cells (LCs), which capture DNTB and migrate to lymph nodes for direct presentation to CD8(+) T cells. Depletion and adoptive transfer experiments revealed that LCs conferred protection from development of CHS by a mechanism involving both anergy and deletion of allergen-specific CD8(+) T cells and activation of a population of T cells identified as ICOS(+)CD4(+)Foxp3(+) Tregs. Our findings highlight the critical role of LCs in tolerance induction in mice to the prototype innocuous hapten DNTB and suggest that strategies targeting LCs might be valuable for prevention of cutaneous allergy.en_GB
dc.language.isoenen
dc.rightsArchived with thanks to The Journal of clinical investigationen_GB
dc.subject.meshAllergensen_GB
dc.subject.meshAnimalsen_GB
dc.subject.meshAntigen Presentationen_GB
dc.subject.meshAntigens, CDen_GB
dc.subject.meshCD8-Positive T-Lymphocytesen_GB
dc.subject.meshCell Communicationen_GB
dc.subject.meshCell Movementen_GB
dc.subject.meshCells, Cultureden_GB
dc.subject.meshDermatitis, Allergic Contacten_GB
dc.subject.meshDinitrobenzenesen_GB
dc.subject.meshEpidermisen_GB
dc.subject.meshForkhead Transcription Factorsen_GB
dc.subject.meshImmune Toleranceen_GB
dc.subject.meshInducible T-Cell Co-Stimulator Proteinen_GB
dc.subject.meshLangerhans Cellsen_GB
dc.subject.meshLymph Nodesen_GB
dc.subject.meshLymphocyte Activationen_GB
dc.subject.meshMiceen_GB
dc.subject.meshMice, Inbred C57BLen_GB
dc.subject.meshMice, Transgenicen_GB
dc.subject.meshT-Lymphocytes, Regulatoryen_GB
dc.titleLangerhans cells protect from allergic contact dermatitis in mice by tolerizing CD8(+) T cells and activating Foxp3(+) regulatory T cells.en
dc.typeArticleen
dc.contributor.departmentINSERM, U851, Lyon, France.en_GB
dc.identifier.journalThe Journal of clinical investigationen_GB

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