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The Skin as a Route of Allergen Exposure: Part I. Immune Components and Mechanisms

  • Allergens (RK Bush and JA Woodfolk, Section Editors)
  • Published:
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Abstract

Purpose of Review

To highlight recent contributions in the literature that enhance our understanding of the cutaneous immune response to allergen.

Recent Findings

Defects in skin barrier function in infancy set the stage for the development of atopic dermatitis (AD) and allergy. Both genetic and environmental factors can contribute to damage of the stratum corneum (SC), with activation of specific protease enzymes under high pH conditions playing a key role. Immune cells and mediators in the dermis and epidermis impair SC repair mechanisms and support allergy development. In barrier-disrupted skin, type 2 innate lymphoid cells (ILC2s), mast cells (MCs), and basophils have been shown to promote AD and pathogenic Th2 responses in murine models.

Summary

Skin barrier disruption favors induction of systemic Th2-associated inflammatory pathways. A better understanding of the ontogeny and regulation of these complex networks in infant skin is needed to guide future strategies for allergy treatment and prevention.

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Abbreviations

AD:

Atopic dermatitis

AMP:

Anti-microbial peptide

APC:

Antigen-presenting cell

CerS3:

Ceramide synthase

CLA:

Cutaneous lymphocyte antigen

DC:

Dendritic cell

DDC:

Dermal dendritic cell

FFA:

Free fatty acids

FLG:

Filaggrin

HDM:

House dust mite

HPV:

Human papilloma virus

iDC:

Inflammatory dendritic cells

IDEC:

Inflammatory dendritic epithelial cell

ILC2:

Type 2 innate lymphoid cell

KLK-5:

Kallikrein-5

KLK-7:

Kallikrein-7

LC:

Langerhans cell

LEKTI:

Kazal-type 5 serine protease inhibitor

LPS:

Lipopolysaccharide

MC:

Mast cell

MDDC:

Monocyte-derived dendritic cell

NMF:

Natural moisturizing factor

OVA:

Ovalbumin

PAR-2:

Protease-activated receptor-2

SC:

Stratum corneum

SCCE:

Stratum corneum chymotryptic enzyme

SKALP:

Skin-derived antileukoprotease

SLS:

Sodium laureth sulfate

SPINK 5:

Serine protease inhibitor kazal-type-5

TER:

Transepithelial resistance

TEWL:

Transepidermal water loss

Tip-DCs:

TNF and iNOS-producing DCs

TJ:

Tight junction

TLR:

Toll-like receptor

Treg:

T regulatory cell

TSLP:

Thymic stromal lymphopoietin

TSLPR:

Thymic stromal lymphopoietin receptor

t-UCA:

Trans urocanic acid

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    Authors and Affiliations

    1. Department of Medicine, University of Virginia School of Medicine, Charlottesville, VA, 22908, USA

      Anna R. Smith, Jeffrey M. Wilson & Julia A. Wisniewski

    2. Department of Public Health Sciences, University of Virginia School of Medicine, Charlottesville, VA, 22908, USA

      George Knaysi

    3. Geisel School of Medicine, Dartmouth College, 1 Rope Ferry Road, Hanover, NH, 03755, USA

      George Knaysi

    4. Department of Pediatrics, University of Virginia School of Medicine, Charlottesville, VA, 22908, USA

      Julia A. Wisniewski

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    1. Anna R. Smith
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    2. George Knaysi
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    4. Julia A. Wisniewski
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    Correspondence to Julia A. Wisniewski.

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    This work was supported by the UVA Child Health Research Grant (J.W.).

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    Drs. Smith, Knaysi, Wilson, and Wisniewski declare no conflicts of interest relevant to this manuscript.

    Human and Animal Rights and Informed Consent

    This article does not contain any studies with human or animal subjects performed by any of the authors.

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    This article is part of the Topical Collection on Allergens

    Anna R. Smith and George Knaysi contributed equally to this work.

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    Smith, A.R., Knaysi, G., Wilson, J.M. et al. The Skin as a Route of Allergen Exposure: Part I. Immune Components and Mechanisms. Curr Allergy Asthma Rep 17, 6 (2017). https://doi.org/10.1007/s11882-017-0674-5

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