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Langerhans cells are critical in epicutaneous sensitization with protein antigen via thymic stromal lymphopoietin receptor signaling.
J Allergy Clin Immunol. 2012 Apr; 129(4):1048-55.e6.JA

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(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.

CONCLUSION

LCs initiate epicutaneous sensitization with protein antigens and induce T(H)2-type immune responses via TSLP signaling.

Authors+Show Affiliations

Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22385635

Citation

Nakajima, Saeko, et al. "Langerhans Cells Are Critical in Epicutaneous Sensitization With Protein Antigen Via Thymic Stromal Lymphopoietin Receptor Signaling." The Journal of Allergy and Clinical Immunology, vol. 129, no. 4, 2012, pp. 1048-55.e6.
Nakajima S, Igyártó BZ, Honda T, et al. Langerhans cells are critical in epicutaneous sensitization with protein antigen via thymic stromal lymphopoietin receptor signaling. J Allergy Clin Immunol. 2012;129(4):1048-55.e6.
Nakajima, S., Igyártó, B. Z., Honda, T., Egawa, G., Otsuka, A., Hara-Chikuma, M., Watanabe, N., Ziegler, S. F., Tomura, M., Inaba, K., Miyachi, Y., Kaplan, D. H., & Kabashima, K. (2012). Langerhans cells are critical in epicutaneous sensitization with protein antigen via thymic stromal lymphopoietin receptor signaling. The Journal of Allergy and Clinical Immunology, 129(4), 1048-e6. https://doi.org/10.1016/j.jaci.2012.01.063
Nakajima S, et al. Langerhans Cells Are Critical in Epicutaneous Sensitization With Protein Antigen Via Thymic Stromal Lymphopoietin Receptor Signaling. J Allergy Clin Immunol. 2012;129(4):1048-55.e6. PubMed PMID: 22385635.
* Article titles in AMA citation format should be in sentence-case
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 - Hara-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, Y1 - 2012/03/03/ PY - 2011/11/25/received PY - 2012/01/09/revised PY - 2012/01/12/accepted PY - 2012/3/6/entrez PY - 2012/3/6/pubmed PY - 2012/7/10/medline SP - 1048 EP - 55.e6 JF - The Journal of allergy and clinical immunology JO - J Allergy Clin Immunol VL - 129 IS - 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(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. CONCLUSION: LCs initiate epicutaneous sensitization with protein antigens and induce T(H)2-type immune responses via TSLP signaling. SN - 1097-6825 UR - https://www.unboundmedicine.com/medline/citation/22385635/Langerhans_cells_are_critical_in_epicutaneous_sensitization_with_protein_antigen_via_thymic_stromal_lymphopoietin_receptor_signaling_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0091-6749(12)00191-1 DB - PRIME DP - Unbound Medicine ER -