Redefining the Role of Langerhans Cells As Immune Regulators within the Skin

Abstract

Langerhans cells (LC) are a unique population of tissue-resident macrophages that form a network of cells across the epidermis of the skin, but which have the ability to migrate from the epidermis to draining lymph nodes (LN). Their location at the skin barrier suggests a key role as immune sentinels. However, despite decades of research, the role of LC in skin immunity is unclear; ablation of LC results in neither fatal susceptibility to skin infection nor overt autoimmunity due to lack of immune regulation. Our understanding of immune processes has traditionally been centered on secondary lymphoid organs as sites of lymphocyte priming and differentiation, which is exemplified by LC, initially defined as a paradigm for tissue dendritic cells that migrate to draining LN on maturation. But, more recently, an awareness of the importance of the tissue environment in shaping effector immunity has emerged. In this mini-review, we discuss whether our lack of understanding of LC function stems from our lymph node-centric view of these cells, and question whether a focus on LC as immune regulators in situ in the skin may reveal clearer answers about their function in cutaneous immunology.

Langerhans Cells: Sensing the Environment in Health and Disease

“…Both keratinocytes and immune cells are essential for sensing the environment and function as a first line of defense against external insults ( 4 ). As such, LCs have proven crucial in various antimicrobial responses, which is reviewed in detail by West et al in this research topic ( 5 ). For long, LCs were considered as the exclusive antigen presenting cells in the skin and a body of literature attributed a role to LCs in the pathogenesis of various skin diseases.…”

Langerhans cells mediate the skin‐induced tolerance to ovalbumin via Langerin in a murine model

“…LCs are epidermis‐resident macrophages with the properties of dendritic cells (DCs) and exert either pro‐inflammatory or immunosuppressive functions, participating in various skin immune responses, for example, defense against pathogen infection, contact hypersensitivity (CHS), epicutaneous sensitization, and UV‐induced inflammation . Many of the studies suggest that the principle function of LCs is to keep homeostasis of the skin . LCs suppress the 2,4‐dinitro‐fluorobenzene‐induced CHS of mice, and the inhibitory effect requires cognate interaction between CD4 + T cells and LCs, and LC‐produced IL‐10 .…”

Memory T cell subsets in healthy gingiva and periodontitis tissues

“…PMNs perform antibacterial functions including phagocytosis, antimicrobial peptide production, and neutrophil extracellular trap formation . Antigen presenting cells including Langerhans cells, tissue dendritic cells, and macrophages have also been demonstrated to have immune regulatory function in maintaining homeostasis . These well‐controlled immune responses in healthy gingiva suppress the plaque bacteria and do not cause overt tissue pathology .…”

“…6 Antigen presenting cells including Langerhans cells, tissue dendritic cells, and macrophages have also been demonstrated to have immune regulatory function in maintaining homeostasis. [7][8][9][10] These well-controlled immune responses in healthy gingiva suppress the plaque bacteria and do not cause overt tissue pathology. 3 Unlike gut, gingiva does not have mucosal lymphoid tissues.…”