Les cellules de Langerhans

Les cellules de Langerhans (CL) de l’épiderme et des épithéliums pluristratifiés appartiennent au système immunitaire. Ces cellules ont un éventail de fonctions très différentes, avec des implications qui vont bien au-delà de la peau, en raison de leurs propriétés de migration qui leur permettent d’informer les lymphocytes T dans les ganglions drainants. Les CL furent longtemps considérées comme les acteurs principaux de la réponse immune dans les maladies infectieuses, tel le sida, l’allergie, les réactions inflammatoires chroniques, les rejets de tumeur ou la transplantation. Découvertes il y a près de 140 ans, elles restent cependant énigmatiques par de nombreux aspects, et leur rôle précis dans le déclenchement de la réaction immunitaire cutanée ou dans l’établissement d’une tolérance aux composants du soi reste controversé.Epidermal Langerhans cells, a constituent of the skin immune system, have a spectrum of different functions with implications that extend far beyond the skin. They have the potential to internalize particulate agents and macromolecules, and display migratory properties that endow them with the unique capacity to journey between skin and draining lymph nodes where they encounter antigen-specific T lymphocytes. In addition, LC are considered to play a pivotal role in infectious disease such as Aids, allergy, chronic inflammatory reactions, tumor rejections or transplantation. Herein, we will review the features of Langerhans cells, emphasizing characteristics representative of their life-cycle stages that occur within the skin

Accumulation of Immature Langerhans Cells in Human Lymph Nodes Draining Chronically Inflamed Skin

The coordinated migration and maturation of dendritic cells (DCs) such as intraepithelial Langerhans cells (LCs) is considered critical for T cell priming in response to inflammation in the periphery. However, little is known about the role of inflammatory mediators for LC maturation and recruitment to lymph nodes in vivo. Here we show in human dermatopathic lymphadenitis (DL), which features an expanded population of LCs in one draining lymph node associated with inflammatory lesions in its tributary skin area, that the Langerin/CD207+ LCs constitute a predominant population of immature DCs, which express CD1a, and CD68, but not CD83, CD86, and DC–lysosomal-associated membrane protein (LAMP)/CD208. Using LC-type cells generated in vitro in the presence of transforming growth factor (TGF)-β1, we further found that tumor necrosis factor (TNF)-α, as a prototype proinflammatory factor, and a variety of inflammatory stimuli and bacterial products, increase Langerin expression and Langerin dependent Birbeck granules formation in cell which nevertheless lack costimulatory molecules, DC–LAMP/CD208 and potent T cell stimulatory activity but express CCR7 and respond to the lymph node homing chemokines CCL19 and CCL21. This indicates that LC migration and maturation can be independently regulated events. We suggest that during DL, inflammatory stimuli in the skin increase the migration of LCs to the lymph node but without associated maturation. Immature LCs might regulate immune responses during chronic inflammation

Targeting self- and foreign antigens to dendritic cells via DC-ASGPR generates IL-10-producing suppressive CD4+ T cells

Dendritic cells (DCs) can initiate and shape host immune responses toward either immunity or tolerance by their effects on antigen-specific CD4(+) T cells. DC-asialoglycoprotein receptor (DC-ASGPR), a lectinlike receptor, is a known scavenger receptor. Here, we report that targeting antigens to human DCs via DC-ASGPR, but not lectin-like oxidized-LDL receptor, Dectin-1, or DC-specific ICAM-3-grabbing nonintegrin favors the generation of antigen-specific suppressive CD4(+) T cells that produce interleukin 10 (IL-10). These findings apply to both self-and foreign antigens, as well as memory and naive CD4(+) T cells. The generation of such IL-10-producing CD4(+) T cells requires p38/extracellular signal-regulated kinase phosphorylation and IL-10 induction in DCs. We further demonstrate that immunization of nonhuman primates with antigens fused to anti-DC-ASGPR monoclonal antibody generates antigen-specific CD4(+) T cells that produce IL-10 in vivo. This study provides a new strategy for the establishment of antigen-specific IL-10-producing suppressive T cells in vivo by targeting whole protein antigens to DCs via DC-ASGPR

External antigen uptake by Langerhans cells with reorganization of epidermal tight junction barriers

Outermost barriers are critical for terrestrial animals to avoid desiccation and to protect their bodies from foreign insults. Mammalian skin consists of two sets of barriers: stratum corneum (SC) and tight junctions (TJs). How acquisition of external antigens (Ags) by epidermal Langerhans cells (LCs) occur despite these barriers has remained unknown. We show that activation-induced LCs elongate their dendrites to penetrate keratinocyte (KC) TJs and survey the extra-TJ environment located outside of the TJ barrier, just beneath the SC. Penetrated dendrites uptake Ags from the tip where Ags colocalize with langerin/Birbeck granules. TJs at KC–KC contacts allow penetration of LC dendrites by dynamically forming new claudin-dependent bicellular- and tricellulin-dependent tricellular TJs at LC–KC contacts, thereby maintaining TJ integrity during Ag uptake. Thus, covertly under keratinized SC barriers, LCs and KCs demonstrate remarkable cooperation that enables LCs to gain access to external Ags that have violated the SC barrier while concomitantly retaining TJ barriers to protect intra-TJ environment

Solitary Type of Congenital Self-healing Reticulohistiocytosis

Congenital self-healing reticulohistiocytosis is a rare, congenital, benign, self-healing variant of Langerhans cell histiocytosis. It usually appears as multiple papules or nodules; however, occurrence of the solitary type is very rare. We report on a case of solitary congenital self-healing reticulohistiocytosis in a 29-day-old girl who presented with a papule on her sole. Two months later, the lesion regressed with a slight scar. Based upon clinical and histologic findings, we made a diagnosis of solitary congenital self-healing reticulohistiocytosis. In this report, we summarized reported cases of solitary congenital self-healing retioculohistiocytosis in Korea with a review of the literature

Langerhans cells are negative regulators of the anti-Leishmania response

Langerhans cells suppress the immune response to low-dose Leishmania major infection in part by inducing regulatory T cells