title: Langerhans cells are critical in epicutaneous sensitization with protein antigen via thymic stromal lymphopoietin receptor signaling.
abstract: BACKGROUND
  The clarification of cutaneous dendritic cell subset and the role of thymic stromal lymphopoietin (TSLP) signaling in epicutaneous sensitization with protein antigens, as in the development of atopic dermatitis, is a crucial issue.
  
  
  OBJECTIVE
  Because TSLP is highly expressed in the vicinity of Langerhans cells (LCs), we sought to clarify our hypothesis that LCs play an essential role in epicutaneous sensitization with protein antigens through TSLP signaling.
  
  
  METHODS
  By using Langerin-diphtheria toxin receptor knock-in mice and human Langerin-diphtheria toxin A transgenic mice, we prepared mice deficient in LCs. We also prepared mice deficient in TSLP receptors in LCs by using TSLP receptor-deficient mice with bone marrow chimeric technique. We applied these mice to an ovalbumin (OVA)-induced epicutaneous sensitization model.
  
  
  RESULTS
  Upon the epicutaneous application of OVA, conditional LC depletion attenuated the development of clinical manifestations as well as serum OVA-specific IgE increase, OVA-specific T-cell proliferation, and IL-4 mRNA expression in the draining lymph nodes. Consistently, even in the steady state, permanent LC depletion resulted in decreased serum IgE levels, suggesting that LCs mediate the T(H)2 local environment. In addition, mice deficient in TSLP receptors on LCs abrogated the induction of OVA-specific IgE levels upon epicutaneous OVA sensitization.
  
  
  CONCLUSIONS
  LCs initiate epicutaneous sensitization with protein antigens and induce T(H)2-type immune responses via TSLP signaling.
authors.affiliation: Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Saeko
authors.initials: S
authors.lastname: Nakajima
authors.forename: Botond Z
authors.initials: BZ
authors.lastname: Igyártó
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Honda
authors.forename: Gyohei
authors.initials: G
authors.lastname: Egawa
authors.forename: Atsushi
authors.initials: A
authors.lastname: Otsuka
authors.forename: Mariko
authors.initials: M
authors.lastname: Hara-Chikuma
authors.forename: Norihiko
authors.initials: N
authors.lastname: Watanabe
authors.forename: Steven F
authors.initials: SF
authors.lastname: Ziegler
authors.forename: Michio
authors.initials: M
authors.lastname: Tomura
authors.forename: Kayo
authors.initials: K
authors.lastname: Inaba
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Miyachi
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Kaplan
authors.forename: Kenji
authors.initials: K
authors.lastname: Kabashima
mesh_terms: D000279:Administration, Cutaneous; D000485:Allergens / Q000008:administration & dosage / Q000276:immunology*; D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism; D018925:Chemokines / Q000096:biosynthesis; D046528:Chimerism; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D017449:Dermatitis, Allergic Contact / Q000276:immunology* / Q000378:metabolism; D004195:Disease Models, Animal; D000939:Epitopes; D005260:Female; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D007801:Langerhans Cells / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053278:OX40 Ligand / Q000378:metabolism; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology*; D018121:Receptors, Cytokine / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D018418:Th2 Cells / Q000276:immunology; D015854:Up-Regulation / Q000276:immunology; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D000485:Allergens; C498762:CRLF2 protein, human; D018925:Chemokines; D016207:Cytokines; D000939:Epitopes; D053278:OX40 Ligand; D018121:Receptors, Cytokine; D007073:Immunoglobulin E; D010047:Ovalbumin; D000094632:Thymic Stromal Lymphopoietin; C000721967:TSLP protein, mouse