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Cutaneous Dendritic Cells in Health and Disease

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Clinical and Basic Immunodermatology

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Abstract

Dendritic cells (DCs) are a heterogeneous cell type found in lymphatic and peripheral tissues. They function as professional antigen-presenting cells (APCs), specialized to acquire antigen from their environment that they process and present to T cells. In addition, DC participate in the generation of local inflammation and suppression of inappropriate immune responses. Thus, they play a critical role in the initiation, propagation and suppression of immune responses that promote health and autoimmune disease. The skin of humans and mice contain several distinct subsets of DC (epidermal Langerhans cells are the most well-known) that are speculated to have varied and versatile functions. In this chapter, we discuss dendritic cells as important players of the innate and adaptive immune system. We will cover their roles in acquiring antigen, inducing T cell responses, and characterizing the functional differences between distinct skin DC subsets. Finally, we will relate DC in relation to human health including their contribution to diseases such as allergic contact dermatitis and psoriasis and their ability to serve as therapeutic targets in vaccinations.

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Author information

Authors and Affiliations

  1. Department of Dermatology, Center for Immunology, University of Minnesota, Minneapolis, MN, USA

    Sakeen W. Kashem

  2. Departments of Dermatology and Immunology, University of Pittsburgh, Pittsburgh, PA, 15261, USA

    Daniel H. Kaplan MD, PhD

Authors
  1. Sakeen W. Kashem
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  2. Daniel H. Kaplan MD, PhD
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Corresponding author

Correspondence to Daniel H. Kaplan MD, PhD .

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

Review Questions

Review Questions

  1. 1.

    Identify the two major subsets of dendritic cells found throughout the secondary lymphoid tissues (select all correct answers).

    1. a.

      IRF8 DC

    2. b.

      Langerhans Cells

    3. c.

      CD103+ dDC

    4. d.

      IRF4 DC

    5. e.

      CD11b + dDC

  • Correct answer: a and d. Classical DCs (broad category of LN/splenic resident DCs) can be broadly categorized into two distinct subsets by the expression of transcriptional factors IRF4 and IRF8. IRF8 cDCs express CD8, XCR1 and Clec9a while IRF4 cDCs express CD11b and CD172. These 2 DC types are found in lymph node, spleen and have closely related counterparts in most peripheral tissues. Skin DCs can be categorized into three broad categories: Langerhans cells, CD11b+ dDCs, and CD103+ dDCs

  1. 2.

    How are dendritic cells activated (select all correct answers)?

    1. a.

      PAMPS

    2. b.

      Cytokines

    3. c.

      Stochastically

    4. d.

      Antigen

    5. e.

      B-catenin

  • Correct answer: a and b. Skin DCs get activated through their pattern recognition receptors (e.g. TLR) as well as by inflammatory cytokines. This results in expression of CCR7 that facilitiates migration into LN and increased expression of MHC-II and co-stimulatory molecules (e.g. B7) that allow for efficient activation of cognate CD4+ and CD8+ T cells

  1. 3.

    What is the function of skin dendritic cells under steady-state conditions (select all correct answers)?

    1. a.

      T cell activation

    2. b.

      Clean-up necrotic debris

    3. c.

      B cell activation

    4. d.

      Inhibition of Mast cell activation

    5. e.

      T cell tolerance

  • Correct answer: e. Steady state DCs mediate tolerance to self antigens through a mechanism involving b-catenin as well as other likely mechanisms

  1. 4.

    What role do dendritic cells play during allergic contact dermatitis, Psoriasis and during infection (select all correct answers)?

    1. a.

      Activate T cells specific for foreign antigens

    2. b.

      Secrete IL-23

    3. c.

      Secrete IL-15

    4. d.

      Induce Th17 responses

    5. e.

      Induce Th2 responses

  • Correct answer: a,b,c,d,e. The precise role of individual DC subsets during allergic contact dermatitis remains unclear. Some studies demonstrate that LCs suppress CHS and DTH while others show that LCs induce CHS and DTH responses. Similarly, the data is also controversial for CD103+ and CD11b+ dDCs. For Psoriasis, mice in which DCs are conditionally depleted have less response in imiquimod induced psoriasis inflammation model. TLR signaling on CD11b+ dDCs have recently been demonstrated to be sufficient in inducing IL-23 in response to imiquimod to drive psoriasis like inflammation in mice. Fo infection, In response to C. albicans, L. major and West Nile virus infections, CD103+ dDCs mediate Th1 responses. LCs mediate Th17 responses in response to epicutaneous C. albicans infection. Finally, CD11b+ dDCs induce Th2 responses to N. brasiliensis infection

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Kashem, S.W., Kaplan, D.H. (2017). Cutaneous Dendritic Cells in Health and Disease. In: Gaspari, A., Tyring, S., Kaplan, D. (eds) Clinical and Basic Immunodermatology. Springer, Cham. https://doi.org/10.1007/978-3-319-29785-9_9

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  • DOI: https://doi.org/10.1007/978-3-319-29785-9_9

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