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Clinical and Basic Immunodermatology pp 1–10Cite as

Innate and Adaptive Components of the Cutaneous Immune Barrier: The Central Role of Dendritic Cells

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Abstract

Immune responses initiated in the skin can be extremely powerful at both a local and systemic level. One of the milestones in elucidating the mechanisms underlying this phenomenon was the discovery of the T cell response-inducing function of Langerhans cells (LC). In the meantime, we know that the family of dendritic antigen-presenting cells in the skin is much bigger and, in addition to LC, includes dermal dendritic cells (DDC), CD141 + DC, CD14 + DC, inflammatory DC and plasmacytoid DC. Depending on the cellular and molecular milieu, these cells can function as either sensitizing or tolerizing elements. Signals transmitted from (innate) receptors recognizing damage- or pathogen-associated patterns are involved in directing these different functions in DC. Toll-like pathogen recognition receptors (TLR) have been particularly well investigated in this regard. The distinct distribution of TLR on LC and other DC subsets allows the immune system to elegantly orchestrate the regulatory and pro-inflammatory functions of these cells. Intriguingly, TLR signaling in DC/LC not only allows to initiate adaptive immune responses, but also directly induces innate effector functions. This is demonstrated by our findings on the mechanisms underlying basal cell carcinoma (BCC) regression upon treatment with the pharmacological TLR7 agonist imiquimod. We observed that in imiquimod-treated BCC, plasmacytoid DC directly kill tumor cells via the apoptosis-inducing molecule TRAIL. Melanoma cells can also become TRAIL-susceptible, but the magnitude of this phenomenon varies from patient to patient. Our recent findings show that TRAIL susceptibility of melanoma cell lines can be increased upon exposure to the anti-inflammatory compound diclofenac.

Taken together, we begin to understand the exact position of LC and DC in the highly complex circuits of the immune system in the skin and how these cells could be manipulated for therapeutic purposes.

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Abbreviations

APC:

Antigen-presenting cell

BCC:

Basal cell carcinoma

CHS:

Contact hypersensitivity

DC:

Dendritic cell

DDC:

Dermal dendritic cell

dsRNA:

Double-strain RNA

LC:

Langerhans cell

LPS:

Lipopolysaccharides

LTA:

Lipotechoic acid

MHC:

Majory histocompatibility complex

PAMP:

Pathogen-associated molecular pattern

pDC:

Plasmacytoid dendritic cell

PRR:

Pattern recognition receptor

S. :

Staphylococcus

ssRNA:

Single-stranded RNA

TLR:

Toll-like receptor

TRAIL:

Tumor necrosis factor related apoptosis inducing ligand

UV:

Ultraviolet

poly I:C:

Polyinosinic:polycytidylic acid

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Author information

Authors and Affiliations

  1. Department of Dermatology, Medical University of Vienna, Vienna, Austria

    Georg Stingl MD

  2. Division of Immunology, Allergy and Infectious Diseases, Department of Dermatology, Medical University of Vienna, Vienna, Austria

    Marie-Charlotte Brüggen MD, PhD & Mariana Vázquez-Strauss MD

Authors
  1. Georg Stingl MD
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  2. Marie-Charlotte Brüggen MD, PhD
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  3. Mariana Vázquez-Strauss MD
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Corresponding author

Correspondence to Georg Stingl MD .

Editor information

Editors and Affiliations

  1. School of Medicine, University of Maryland Baltimore, Baltimore, Maryland, USA

    Anthony A. Gaspari

  2. Department of Dermatology, University of Texas Health Science Center, Houston, Texas, USA

    Stephen K. Tyring

  3. Department of Dermatology and Immunology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA

    Daniel H. Kaplan

Questions

Questions

  1. 1.

    Which one of the following statements on LC in the skin is correct?

    1. A.

      UV-irradiation and the treatment with corticosteroids enhance the ability of LCs to induce cytotoxic T cell responses

    2. B.

      LC are exclusive stimulators of Th1 cells

    3. C.

      Under certain conditions, LC can induce the expansion of Tregs and down-regulate proliferative and cytotoxic T cell responses

    4. D.

      In contrast to keratinocytes, LC cannot produce any inflammatory cytokines

    5. E.

      LC are found in the dermis but not in the epidermis

  2. 2.

    Which statement regarding TLR is true?

    1. A.

      TLR are exclusively expressed on cells of hematopoietic origin

    2. B.

      While TLR signaling is a major modulator of innate immune responses, it does not have any effect on adaptive immune responses

    3. C.

      TLR recognizing lipids are located on the outer cell membrane while those recognizing proteins are found intracellularly

    4. D.

      The different DC subsets in skin express the same TLR repertoire

    5. E.

      TLR belong to the PRR family that includes receptors recognizing damage- and pathogen-associated molecular patterns

  3. 3.

    Which statement does not describe parts of the mechanism underlying the imiquimod-induced clinical regression of BCC?

    1. A.

      Imiquimod acts as an artificial TLR7-ligand

    2. B.

      Imiquimod induces pDC to kill BCC cells in a mostly TRAIL-mediated fashion

    3. C.

      Imiquimod induces the killer molecule TRAIL on peripheral blood pDC in an IFN-α-dependent manner

    4. D.

      Imiquimod-treated BCC become selectively infiltrated by NK cells

    5. E.

      Imiquimod application leads to the apoptosis of BCC cancer cells

Answers

  1. 1.

    C

  2. 2.

    E

  3. 3.

    D

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Stingl, G., Brüggen, MC., Vázquez-Strauss, M. (2017). Innate and Adaptive Components of the Cutaneous Immune Barrier: The Central Role of Dendritic Cells. In: Gaspari, A., Tyring, S., Kaplan, D. (eds) Clinical and Basic Immunodermatology. Springer, Cham. https://doi.org/10.1007/978-3-319-29785-9_1

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  • DOI: https://doi.org/10.1007/978-3-319-29785-9_1

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  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-29783-5

  • Online ISBN: 978-3-319-29785-9

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