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The immunological anatomy of the skin

Nature Reviews Immunology volume 19, pages 19–30 (2019)Cite this article

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Abstract

The skin is the outermost organ of the body and is continuously exposed to external pathogens. Upon inflammation, various immune cells pass through, reside in or are recruited to the skin to orchestrate diverse cutaneous immune responses. To achieve this, immune cells interact with each other and even communicate with non-immune cells, including peripheral nerves and the microbiota. Immunologically important anatomical sites, such as skin appendages (for example, hair follicles and sweat glands) or postcapillary venules, act as special portal sites for immune cells and for establishing tertiary lymphoid structures, including inducible skin-associated lymphoid tissue. Here, we provide an overview of the key findings and concepts of cutaneous immunity in association with skin anatomy and discuss how cutaneous immune cells fine-tune physiological responses in the skin.

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Fig. 1: Physical and immunological barrier of the skin.
Fig. 2: A specific contribution of postcapillary venules in cutaneous immunity.
Fig. 3: Neuro-immune interactions and perivascular adipose tissue in the skin.
Fig. 4: Penetration of hapten and proteins into the skin.
Fig. 5: A schematic view of the sensitization and elicitation phases of contact hypersensitivity.
Fig. 6: Newly identified key locations and structures in skin immunity.

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Acknowledgements

This work was supported by grants from the Japan Society for the Promotion of Science KAKENHI (JP15K09766, JP15H05096 (to T.H.) and 263395 (to K.K)), Grants-in-Aid for Scientific Research (15H05790, 15H1155 and 15K15417 to K.K.) and the Japan Agency for Medical Research and Development (AMED) (16ek0410011h0003 and 16he0902003h0002 to K.K.). The authors thank A. Hayday of the King’s College London School of Medicine, London, UK, and E. Epstein Jr of PellePharm for the critical reading of the manuscript.

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Nature Reviews Immunology thanks B. Malissen and the other anonymous reviewer(s) for their contribution to the peer review of this work.

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Authors and Affiliations

  1. Department of Dermatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan

    Kenji Kabashima, Tetsuya Honda & Gyohei Egawa

  2. Singapore Immunology Network (SIgN) and Institute of Medical Biology (IMB), Agency for Science, Technology and Research (A*STAR), Biopolis, Singapore

    Kenji Kabashima & Florent Ginhoux

  3. Shanghai Institute of Immunology, Shanghai JiaoTong University School of Medicine, Shanghai, China

    Florent Ginhoux

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All authors contributed to the discussion of the content of the article. G.E. and T.H. also contributed to researching data and the writing of the article. K.K. and F.G. also contributed to the review and editing of the manuscript.

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Glossary

Langerin-DTR mice

Mice that express diphtheria toxin receptor (DTR) under the control of the Langerin gene promoter. Treatment of these mice with diphtheria toxin leads to the deletion of all Langerin-expressing cells.

Alopecia areata

A patchy hair loss mainly occurring in the scalp. It is believed to be one of the autoimmune diseases.

Eosinophilic pustular folliculitis

A recurrent folliculitis that is often formed in the face. In this condition, many eosinophils are pathologically accumulated around hair follicles.

Transient receptor potential subfamily V member 1

(TRPV1). Also known as capsaicin receptor; TRPV1 is a cation channel member selectively expressed on peripheral sensory neurons that serves as a molecular sensor (nociceptor) for noxious stimuli.

Trogocytosis

Lymphocytes that conjugate to antigen-presenting cells sometimes ‘rob’ the surface molecules and express them on their own surfaces. ‘Trogo’ means ‘gnaw’ in Greek.

Kimura disease

A chronic inflammatory disorder characterized by a painless lymphadenopathy or masses on head and neck regions.

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Kabashima, K., Honda, T., Ginhoux, F. et al. The immunological anatomy of the skin. Nat Rev Immunol 19, 19–30 (2019). https://doi.org/10.1038/s41577-018-0084-5

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  • DOI: https://doi.org/10.1038/s41577-018-0084-5

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