Langerhans cells utilize CD1a and langerin to efficiently present nonpeptide antigens to T cells

Hunger, Robert E.; Sieling, Peter A.; Ochoa, María Teresa; Sugaya, Makoto; Burdick, Anne E.; Rea, Thomas H.; Brennan, Patrick J.; Belisle, John T.; Blauvelt, Andrew; Porcelli, Steven A.; Modlin, Robert L.

doi:10.1172/jci200419655

Cited by 243 publications

(110 citation statements)

References 45 publications

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“…In vitro studies have shown that Langerhans cells take up and process lipid antigens and microbial fragments for presentation to effector T cells52. In addition, human Langerhans cells have been shown to preferentially induce the differentiation of T H 2 cells and can prime and cross-prime naive CD8 + T cells53.…”

Section: Skin-resident Dcs As Immune Sentinelsmentioning

confidence: 99%

Skin immune sentinels in health and disease

Nestle¹,

Meglio²,

Qin³

et al. 2009

Nat Rev Immunol

1,107

991

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Human skin and its immune cells provide essential protection of the human body from injury and infection. Recent studies reinforce the importance of keratinocytes as sensors of danger through alert systems such as the inflammasome. In addition, newly identified CD103 + dendritic cells are strategically positioned for cross-presentation of skin-tropic pathogens and accumulating data highlight a key role of tissue-resident rather than circulating T cells in skin homeostasis and pathology. This Review focuses on recent progress in dissecting the functional role of skin immune cells in skin disease.The skin, as the primary interface between the body and the environment, provides a first line of defence against microbial pathogens and physical and chemical insults. Immunosurveillance of such a large and exposed organ presents unique challenges for immune sentinels and effector cells. If an immune response is inadequate then overwhelming infections or tumours may ensue, but if an immune response is excessive then chronic inflammation and autoimmunity may develop. Controlling the extent of an immune response is thus a major challenge for maintaining skin integrity, which is of paramount importance for host survival. Therefore, both active defence mechanisms and tolerogenic pathways are used by the host to achieve immune homeostasis, ensuring that immune responses in the skin are properly adjusted to various challenges.Owing to its accessibility, the skin is an ideal organ system in which to study both tissue and whole-organism responses to local and systemic insults. A growing body of data supports the notion that the skin has essential immunological functions, both during tissue homeostasis and in various pathological conditions. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptAlthough early studies highlighted individual cell types in the skin, it was the visionary concept of the skin-associated lymphoid tissue (SALT), first described by Streilein in 1983 (REF. 1 ), and later the 'skin immune system' (REF. 2 ) that provided a modern interpretation and overall paradigm for investigators interested in cutaneous immunology. The initial SALT concept introduced the idea of distinct circuiting immune cells that continually traffic in a directed manner between the skin, the draining lymph nodes and the circulation, thereby providing optimal immunosurveillance.Although considerable attention was directed at the function of epidermal Langerhans cells 3 , it became apparent that other types of dendritic cells (DCs) and innate immune cells present in the dermis also have a relevant role, resulting in the emergence of the concept of a 'dermal immune system' (REF. 4 ). Human skin has two main compartments: the epidermis and the dermis (FIG. 1). The epidermis is the outer compartment and contains four strata. The stratum basale is the bottom layer of the epidermis and is responsible for constantly renewing the cells of the epidermis. This layer contains just one row of undifferentiated epidermal ...

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Section: Skin-resident Dcs As Immune Sentinelsmentioning

confidence: 99%

Skin immune sentinels in health and disease

Nestle¹,

Meglio²,

Qin³

et al. 2009

Nat Rev Immunol

1,107

991

View full text Add to dashboard Cite

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“…Human LCs express CD1a and CD1c molecules, whereas DDCs lack Langerin and BG, and express CD1b molecules and macrophage mannose receptors (Brigl and Brenner 6 LARREGINA AND FALO THE JOURNAL OF INVESTIGATIVE DERMATOLOGY 2004;Mizumoto and Takashima, 2004). Recent studies have demonstrated that these cellular structures and molecules are not only differential markers for LCs and DDCs, but are important functionally as interrelated components of the Ag processing and presenting machinery in the context of CD1 molecules (Hunger et al, 2004).…”

Section: The Emerging Role Of Skin Dendritic Cells In the Presentatiomentioning

confidence: 99%

Changing Paradigms in Cutaneous Immunology: Adapting with Dendritic Cells

Larregina

Falo

2005

Journal of Investigative Dermatology

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“…Two main types of DCs are found in noninflamed skin: epidermal Langerhans cells (LCs) and dermal DCs (1,2). LCs express Langerin/CD207, an endocytic receptor that localizes to and forms Birbeck granules, as well as the CD1a class I-like molecule that presents glycolipids (3). Dermal DCs have long been defined on the basis of expression of a clotting factor, the transglutaminase factor XIIIA (FXIIIA) (4).…”

Section: Introductionmentioning

confidence: 99%

Normal human dermis contains distinct populations of CD11c+BDCA-1+ dendritic cells and CD163+FXIIIA+ macrophages

Zaba¹,

Fuentes‐Duculan²,

Steinman³

et al. 2007

J. Clin. Invest.

267

312

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We used a panel of monoclonal antibodies to characterize DCs in the dermis of normal human skin. Staining for the CD11c integrin, which is abundant on many kinds of DCs, revealed cells in the upper dermis. These cells were positive for blood DC antigen-1 (BDCA-1; also known as CD1c), HLA-DR, and CD45, markers that are also expressed by circulating myeloid DCs. A small subset of CD11c + dermal cells expressed DEC-205/ CD205 and DC-lysosomal-associated membrane glycoprotein/CD208 (DC-LAMP/CD208), suggesting some differentiation or maturation. When BDCA-1 + cells were selected from collagenase digests of normal dermis, they proved to be strong stimulators for T cells in a mixed leukocyte reaction. A second major population of cells located throughout the dermis was positive for factor XIIIA (FXIIIA), but lacked CD11c and BDCA-1. They expressed the macrophage scavenger receptor CD163 and stained weakly for HLA-DR and CD45. Isolated CD163 + dermal cells were inactive in stimulating T cell proliferation, but in biopsies of tattoos, these cells were selectively laden with granular pigments. Plasmacytoid DCs were also present in the dermis, marked by CD123 and BDCA-2. In summary, the normal dermis contains typical immunostimulatory myeloid DCs identified by CD11c and BDCA-1, as well as an additional population of poorly stimulatory macrophages marked by CD163 and FXIIIA.

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Langerhans cells utilize CD1a and langerin to efficiently present nonpeptide antigens to T cells

Cited by 243 publications

References 45 publications

Skin immune sentinels in health and disease

Skin immune sentinels in health and disease

Changing Paradigms in Cutaneous Immunology: Adapting with Dendritic Cells

Normal human dermis contains distinct populations of CD11c+BDCA-1+ dendritic cells and CD163+FXIIIA+ macrophages

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