Disruption of the<i>langerin</i>/<i>CD207</i>Gene Abolishes Birbeck Granules without a Marked Loss of Langerhans Cell Function

Kissenpfennig, Adrien; Aït-Yahia, Smina; Clair-Moninot, Valérie; Stössel, Hella; Badell, Edgar; Bordat, Yann; Pooley, Joanne; Lang, Thierry; Prina, Éric; Coste, Isabelle; Gresser, Olivia; Renno, Toufic; Winter, Nathalie; Milon, Geneviève; Shortman, Ken; Romani, Nikolaus; Lebecque, Serge; Malissen, Bernard; Saeland, Sem; Douillard, Patrice

doi:10.1128/mcb.25.1.88-99.2005

Cited by 103 publications

(93 citation statements)

References 84 publications

(85 reference statements)

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“…In TbR1-deficient LCs, this upregulation of Langerin was diminished. Notably, this by itself does not alter LC function or differentiation as has been demonstrated in Langerin knockout animals (45). Rather, it supports the crucial role of TGF-b in the induction of Langerin expression by LCs (3).…”

Section: Discussionmentioning

confidence: 60%

TGF-β Is Required To Maintain the Pool of Immature Langerhans Cells in the Epidermis

Kel

Girard-Madoux

Reizis

et al. 2010

The Journal of Immunology

151

142

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Section: Discussionmentioning

confidence: 60%

TGF-β Is Required To Maintain the Pool of Immature Langerhans Cells in the Epidermis

Kel

Girard-Madoux

Reizis

et al. 2010

The Journal of Immunology

151

142

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“…Thus the discovery of Langerin, a C-type lectin expressed by LC that is responsible for the generation of Birbeck granules, which are the ultrastructural hallmark of LC, was met with great excitement [26]. Although Langerin is dispensable for LC development [27], the identification of a gene that is selectively expressed by LC proved quite valuable and was exploited by our three groups (B.C. : Dutch group; A.K.…”

Section: Generation Of Three Lc-deficient Mouse Modelsmentioning

confidence: 99%

Insights into Langerhans cell function from Langerhans cell ablation models

2008

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Langerhans cells (LC) are the principal dendritic cell (DC) population in the epidermis of the skin. Owing to their prominent position at the environmental barrier, LC have long been considered to be prototypic sentinel DC. More recently, the precise role of LC in the initiation and control of cutaneous immune responses has become debatable. To elucidate their contribution to immune regulation in the skin, our laboratories have generated genetically modified mice in which LC can be followed in situ by expression of enhanced green fluorescent protein and can be either inducibly or constitutively depleted in vivo. This review highlights the similarities and differences between these mouse models, discusses the discovery and functional significance of Langerin 1 dermal DC, and examines some recent data that help to shed light on LC function. The Langerhans cell paradigmLangerhans cells (LC) were discovered by Paul Langerhans in 1868 [1], but it took more than 100 years before they were first associated with the immune system and recognized as antigenpresenting cells [2]. In particular, Ralph Steinman's group [3] dissected the functional characteristics of LC starting from the seminal finding that murine epidermal LC mature into potent immunostimulatory dendritic cells (DC) in vitro. The work that followed shaped the concept of DC as professional inducers of T-cell immune responses largely by studying LC, though the term 'LC paradigm' was coined much later by Wilson and Villadangos [4].This concept assigned three key functions to LC/DC (reviewed in [5]). First, immature LC that reside in the periphery in the steady state are highly specialized in antigen uptake. LC form a dense network in the epidermis where they constantly scan the environment by extending and retracting their dendrites and are ideally positioned to detect any pathogen breaching the skin barrier [6]. Second, LC transport antigen to skindraining lymph nodes (LN), which is essential to ensure interaction with rare antigen-specific naive T cells. Stimulation by a number of pathogen products in addition to pro-inflammatory cytokines induces LC activation [7][8][9]. Activated LC downregulate expression of E-cadherin, which is thought to maintain their position in the epidermis, and begin to express CC Correspondence: Daniel Kaplan e-mail: DanKaplan@umn.edu Eur. J. Immunol. 2008. 38: 2369-2376 DOI 10.1002 HIGHLIGHTS 2369 Mini-Reviewwww.eji-journal.eu chemokine receptor 7, which guides the cells to the T-cell areas in the LN. Third, during migration the LC undergo a process of maturation in which they process antigen acquired in the skin and present it in the context of MHC class I/II. In addition, they dramatically upregulate their surface expression of co-stimulatory molecules and start to produce cytokines required for proper Th1 or Th2 instruction. Thus, by the time LC arrive in the LN, they have acquired the surface phenotype of a 'functionally' mature DC capable of activating naive T cells and thereby initiating an adaptive immune response specif...

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“…LC express langerin (CD207), a type II membrane-associated C-type lectin that binds mannose residues via a single carbohydrate recognition domain (19). Langerin-deficient mice lack BG, and introduction of the langerin gene into fibroblasts induces the formation of BG, suggesting that langerin has a formative role in BG structure (19,20). In the steady state, langerin is retained primarily in endosomal recycling compartments, and BG form apparently where langerin accumulates in pericentriolar endosomes (21).…”

Section: Angerhans Cells (Lc)mentioning

confidence: 99%

Estrogen Selectively Promotes the Differentiation of Dendritic Cells with Characteristics of Langerhans Cells

Mao¹,

Paharkova-Vatchkova²,

Hardy

et al. 2005

The Journal of Immunology

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The steroid hormone estrogen regulates the differentiation, survival, or function of diverse immune cells. Previously, we found that physiological amounts of 17β-estradiol act via estrogen receptors (ER) to promote the GM-CSF-mediated differentiation of dendritic cells (DC) from murine bone marrow progenitors in ex vivo cultures. Of the two major subsets of CD11c+ DC that develop in these cultures, estrogen is preferentially required for the differentiation of a CD11bintLy6C− population, although it also promotes increased numbers of a CD11bhighLy6C+ population. Although both DC subsets express ERα, only the CD11bhighLy6C+ DC express ERβ, perhaps providing a foundation for the differential regulation of these two DC types by estrogen. The two DC populations exhibit distinct phenotypes in terms of capacity for costimulatory molecule and MHC expression, and Ag internalization, which predict functional differences. The CD11bintLy6C− population shows the greatest increase in MHC and CD86 expression after LPS activation. Most notably, the estrogen-dependent CD11bintLy6C− DC express langerin (CD207) and contain Birbeck granules characteristic of Langerhans cells. These data show that estrogen promotes a DC population with the unique features of epidermal Langerhans cells and suggest that differentiation of Langerhans cells in vivo will be dependent upon local estrogen levels and ER-mediated signaling events in skin.

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Disruption of thelangerin/CD207Gene Abolishes Birbeck Granules without a Marked Loss of Langerhans Cell Function

Cited by 103 publications

References 84 publications

TGF-β Is Required To Maintain the Pool of Immature Langerhans Cells in the Epidermis

TGF-β Is Required To Maintain the Pool of Immature Langerhans Cells in the Epidermis

Insights into Langerhans cell function from Langerhans cell ablation models

Estrogen Selectively Promotes the Differentiation of Dendritic Cells with Characteristics of Langerhans Cells

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