Langerhans cells are critical in epicutaneous sensitization with protein antigen via thymic stromal lymphopoietin receptor signaling

Saeko Nakajima, Botond Z. Igyártó, Tetsuya Honda, Gyohei Egawa, Atsushi Otsuka, Mariko Chikuma, Norihiko Watanabe, Steven F. Ziegler, Michio Tomura, Kayo Inaba, Yoshiki Miyachi, Daniel H. Kaplan, Kenji Kabashima

Research output: Contribution to journalArticle

134 Citations (Scopus)

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. Objectives: 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 H2 local environment. In addition, mice deficient in TSLP receptors on LCs abrogated the induction of OVA-specific IgE levels upon epicutaneous OVA sensitization. Conclusion: LCs initiate epicutaneous sensitization with protein antigens and induce T H2-type immune responses via TSLP signaling.

Original languageEnglish
JournalJournal of Allergy and Clinical Immunology
Volume129
Issue number4
DOIs
Publication statusPublished - 2012 Apr
Externally publishedYes

Fingerprint

Langerhans Cells
Ovalbumin
Antigens
Proteins
Immunoglobulin E
thymic stromal lymphopoietin
Diphtheria Toxin
Viral Tumor Antigens
Atopic Dermatitis
Serum
Interleukin-4
Transgenic Mice
Lymph Nodes
Bone Marrow
Cell Proliferation
T-Lymphocytes
Messenger RNA

Keywords

  • epicutaneous sensitization
  • Langerhans cell
  • protein antigen
  • TSLP
  • TSLP receptor

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Langerhans cells are critical in epicutaneous sensitization with protein antigen via thymic stromal lymphopoietin receptor signaling. / Nakajima, Saeko; Igyártó, Botond Z.; Honda, Tetsuya; Egawa, Gyohei; Otsuka, Atsushi; Chikuma, Mariko; Watanabe, Norihiko; Ziegler, Steven F.; Tomura, Michio; Inaba, Kayo; Miyachi, Yoshiki; Kaplan, Daniel H.; Kabashima, Kenji.

In: Journal of Allergy and Clinical Immunology, Vol. 129, No. 4, 04.2012.

Research output: Contribution to journalArticle

Nakajima, S, Igyártó, BZ, Honda, T, Egawa, G, Otsuka, A, Chikuma, M, Watanabe, N, Ziegler, SF, Tomura, M, Inaba, K, Miyachi, Y, Kaplan, DH & Kabashima, K 2012, 'Langerhans cells are critical in epicutaneous sensitization with protein antigen via thymic stromal lymphopoietin receptor signaling', Journal of Allergy and Clinical Immunology, vol. 129, no. 4. https://doi.org/10.1016/j.jaci.2012.01.063
Nakajima, Saeko ; Igyártó, Botond Z. ; Honda, Tetsuya ; Egawa, Gyohei ; Otsuka, Atsushi ; Chikuma, Mariko ; Watanabe, Norihiko ; Ziegler, Steven F. ; Tomura, Michio ; Inaba, Kayo ; Miyachi, Yoshiki ; Kaplan, Daniel H. ; Kabashima, Kenji. / Langerhans cells are critical in epicutaneous sensitization with protein antigen via thymic stromal lymphopoietin receptor signaling. In: Journal of Allergy and Clinical Immunology. 2012 ; Vol. 129, No. 4.
@article{b9728c5794104f56800dc5ecc026f7ef,
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. Objectives: 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 H2 local environment. In addition, mice deficient in TSLP receptors on LCs abrogated the induction of OVA-specific IgE levels upon epicutaneous OVA sensitization. Conclusion: LCs initiate epicutaneous sensitization with protein antigens and induce T H2-type immune responses via TSLP signaling.",
keywords = "epicutaneous sensitization, Langerhans cell, protein antigen, TSLP, TSLP receptor",
author = "Saeko Nakajima and Igy{\'a}rt{\'o}, {Botond Z.} and Tetsuya Honda and Gyohei Egawa and Atsushi Otsuka and Mariko Chikuma and Norihiko Watanabe and Ziegler, {Steven F.} and Michio Tomura and Kayo Inaba and Yoshiki Miyachi and Kaplan, {Daniel H.} and Kenji Kabashima",
year = "2012",
month = "4",
doi = "10.1016/j.jaci.2012.01.063",
language = "English",
volume = "129",
journal = "Journal of Allergy and Clinical Immunology",
issn = "0091-6749",
publisher = "Mosby Inc.",
number = "4",

}

TY - JOUR

T1 - Langerhans cells are critical in epicutaneous sensitization with protein antigen via thymic stromal lymphopoietin receptor signaling

AU - Nakajima, Saeko

AU - Igyártó, Botond Z.

AU - Honda, Tetsuya

AU - Egawa, Gyohei

AU - Otsuka, Atsushi

AU - Chikuma, Mariko

AU - Watanabe, Norihiko

AU - Ziegler, Steven F.

AU - Tomura, Michio

AU - Inaba, Kayo

AU - Miyachi, Yoshiki

AU - Kaplan, Daniel H.

AU - Kabashima, Kenji

PY - 2012/4

Y1 - 2012/4

N2 - 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. Objectives: 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 H2 local environment. In addition, mice deficient in TSLP receptors on LCs abrogated the induction of OVA-specific IgE levels upon epicutaneous OVA sensitization. Conclusion: LCs initiate epicutaneous sensitization with protein antigens and induce T H2-type immune responses via TSLP signaling.

AB - 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. Objectives: 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 H2 local environment. In addition, mice deficient in TSLP receptors on LCs abrogated the induction of OVA-specific IgE levels upon epicutaneous OVA sensitization. Conclusion: LCs initiate epicutaneous sensitization with protein antigens and induce T H2-type immune responses via TSLP signaling.

KW - epicutaneous sensitization

KW - Langerhans cell

KW - protein antigen

KW - TSLP

KW - TSLP receptor

UR - http://www.scopus.com/inward/record.url?scp=84859158015&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84859158015&partnerID=8YFLogxK

U2 - 10.1016/j.jaci.2012.01.063

DO - 10.1016/j.jaci.2012.01.063

M3 - Article

C2 - 22385635

AN - SCOPUS:84859158015

VL - 129

JO - Journal of Allergy and Clinical Immunology

JF - Journal of Allergy and Clinical Immunology

SN - 0091-6749

IS - 4

ER -