Tags

Type your tag names separated by a space and hit enter

Spontaneous atopic dermatitis is mediated by innate immunity, with the secondary lung inflammation of the atopic march requiring adaptive immunity.
J Allergy Clin Immunol 2016; 137(2):482-91JA

Abstract

BACKGROUND

Atopic dermatitis (AD) is an inflammatory skin condition that can occur in early life, predisposing to asthma development in a phenomenon known as the atopic march. Although genetic and environmental factors are known to contribute to AD and asthma, the mechanisms underlying the atopic march remain poorly understood. Filaggrin loss-of-function mutations are a major genetic predisposer for the development of AD and progression to AD-associated asthma.

OBJECTIVE

We sought to experimentally address whether filaggrin mutations in mice lead to the development of spontaneous eczematous inflammation and address the aberrant immunologic milieu arising in a mouse model of filaggrin deficiency.

METHODS

Filaggrin mutant mice were generated on the proallergic BALB/c background, creating a novel model for the assessment of spontaneous AD-like inflammation. Independently recruited AD case collections were analyzed to define associations between filaggrin mutations and immunologic phenotypes.

RESULTS

Filaggrin-deficient mice on a BALB/c background had profound spontaneous AD-like inflammation with progression to compromised pulmonary function with age, reflecting the atopic march in patients with AD. Strikingly, skin inflammation occurs independently of adaptive immunity and is associated with cutaneous expansion of IL-5-producing type 2 innate lymphoid cells. Furthermore, subjects with filaggrin mutations have an increased frequency of type 2 innate lymphoid cells in the skin in comparison with control subjects.

CONCLUSION

This study provides new insights into our understanding of the atopic march, with innate immunity initiating dermatitis and the adaptive immunity required for subsequent development of compromised lung function.

Authors+Show Affiliations

Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland; National Children's Research Centre, Our Lady's Children's Hospital, Dublin, Ireland.Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland; National Children's Research Centre, Our Lady's Children's Hospital, Dublin, Ireland.Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland; National Children's Research Centre, Our Lady's Children's Hospital, Dublin, Ireland.Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland; National Children's Research Centre, Our Lady's Children's Hospital, Dublin, Ireland.Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland; National Children's Research Centre, Our Lady's Children's Hospital, Dublin, Ireland.MRC Human Immunology Unit, NIHR Biomedical Research Centre, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom.Institute of Molecular Medicine, St James's Hospital, Dublin, Ireland.MRC Laboratory of Molecular Biology, Cambridge, United Kingdom; Biosceptre, Babraham Research Campus, Babraham, Cambridge, United Kingdom.Department of Pathology and Comprehensive Cancer Center, University of Michigan, Ann Arbor, Mich.Institute of Molecular Medicine, St James's Hospital, Dublin, Ireland.Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland; National Children's Research Centre, Our Lady's Children's Hospital, Dublin, Ireland.National Children's Research Centre, Our Lady's Children's Hospital, Dublin, Ireland; Department of Paediatric Dermatology, Our Lady's Children's Hospital, Dublin, Ireland.MRC Laboratory of Molecular Biology, Cambridge, United Kingdom.MRC Human Immunology Unit, NIHR Biomedical Research Centre, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom.Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland; National Children's Research Centre, Our Lady's Children's Hospital, Dublin, Ireland; Institute of Molecular Medicine, St James's Hospital, Dublin, Ireland. Electronic address: pfallon@tcd.ie.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26299987

Citation

Saunders, Sean P., et al. "Spontaneous Atopic Dermatitis Is Mediated By Innate Immunity, With the Secondary Lung Inflammation of the Atopic March Requiring Adaptive Immunity." The Journal of Allergy and Clinical Immunology, vol. 137, no. 2, 2016, pp. 482-91.
Saunders SP, Moran T, Floudas A, et al. Spontaneous atopic dermatitis is mediated by innate immunity, with the secondary lung inflammation of the atopic march requiring adaptive immunity. J Allergy Clin Immunol. 2016;137(2):482-91.
Saunders, S. P., Moran, T., Floudas, A., Wurlod, F., Kaszlikowska, A., Salimi, M., ... Fallon, P. G. (2016). Spontaneous atopic dermatitis is mediated by innate immunity, with the secondary lung inflammation of the atopic march requiring adaptive immunity. The Journal of Allergy and Clinical Immunology, 137(2), pp. 482-91. doi:10.1016/j.jaci.2015.06.045.
Saunders SP, et al. Spontaneous Atopic Dermatitis Is Mediated By Innate Immunity, With the Secondary Lung Inflammation of the Atopic March Requiring Adaptive Immunity. J Allergy Clin Immunol. 2016;137(2):482-91. PubMed PMID: 26299987.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Spontaneous atopic dermatitis is mediated by innate immunity, with the secondary lung inflammation of the atopic march requiring adaptive immunity. AU - Saunders,Sean P, AU - Moran,Tara, AU - Floudas,Achilleas, AU - Wurlod,Felicity, AU - Kaszlikowska,Agnieszka, AU - Salimi,Maryam, AU - Quinn,Emma M, AU - Oliphant,Christopher J, AU - Núñez,Gabriel, AU - McManus,Ross, AU - Hams,Emily, AU - Irvine,Alan D, AU - McKenzie,Andrew N J, AU - Ogg,Graham S, AU - Fallon,Padraic G, Y1 - 2015/08/20/ PY - 2014/11/13/received PY - 2015/05/09/revised PY - 2015/06/15/accepted PY - 2015/8/25/entrez PY - 2015/8/25/pubmed PY - 2016/7/1/medline KW - Allergy KW - asthma KW - atopic dermatitis KW - atopy KW - eczema KW - filaggrin KW - flaky tail KW - innate immunity KW - mouse KW - mutation KW - type 2 innate lymphoid cells SP - 482 EP - 91 JF - The Journal of allergy and clinical immunology JO - J. Allergy Clin. Immunol. VL - 137 IS - 2 N2 - BACKGROUND: Atopic dermatitis (AD) is an inflammatory skin condition that can occur in early life, predisposing to asthma development in a phenomenon known as the atopic march. Although genetic and environmental factors are known to contribute to AD and asthma, the mechanisms underlying the atopic march remain poorly understood. Filaggrin loss-of-function mutations are a major genetic predisposer for the development of AD and progression to AD-associated asthma. OBJECTIVE: We sought to experimentally address whether filaggrin mutations in mice lead to the development of spontaneous eczematous inflammation and address the aberrant immunologic milieu arising in a mouse model of filaggrin deficiency. METHODS: Filaggrin mutant mice were generated on the proallergic BALB/c background, creating a novel model for the assessment of spontaneous AD-like inflammation. Independently recruited AD case collections were analyzed to define associations between filaggrin mutations and immunologic phenotypes. RESULTS: Filaggrin-deficient mice on a BALB/c background had profound spontaneous AD-like inflammation with progression to compromised pulmonary function with age, reflecting the atopic march in patients with AD. Strikingly, skin inflammation occurs independently of adaptive immunity and is associated with cutaneous expansion of IL-5-producing type 2 innate lymphoid cells. Furthermore, subjects with filaggrin mutations have an increased frequency of type 2 innate lymphoid cells in the skin in comparison with control subjects. CONCLUSION: This study provides new insights into our understanding of the atopic march, with innate immunity initiating dermatitis and the adaptive immunity required for subsequent development of compromised lung function. SN - 1097-6825 UR - https://www.unboundmedicine.com/medline/citation/26299987/Spontaneous_atopic_dermatitis_is_mediated_by_innate_immunity_with_the_secondary_lung_inflammation_of_the_atopic_march_requiring_adaptive_immunity_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0091-6749(15)01022-2 DB - PRIME DP - Unbound Medicine ER -