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A Langerhans cell (LC) is a tissue-resident
macrophage Macrophages (abbreviated as M φ, MΦ or MP) ( el, large eaters, from Greek ''μακρός'' (') = large, ''φαγεῖν'' (') = to eat) are a type of white blood cell of the immune system that engulfs and digests pathogens, such as cancer cell ...
of the skin. These cells contain organelles called Birbeck granules. They are present in all layers of the
epidermis The epidermis is the outermost of the three layers that comprise the skin, the inner layers being the dermis and hypodermis. The epidermis layer provides a barrier to infection from environmental pathogens and regulates the amount of water relea ...
and are most prominent in the
stratum spinosum The stratum spinosum (or spinous layer/prickle cell layer) is a layer of the epidermis found between the stratum granulosum and stratum basale. This layer is composed of polyhedral keratinocytes. These are joined with desmosomes. Their spiny (Latin ...
. They also occur in the
papillary dermis The dermis or corium is a layer of skin between the epidermis (with which it makes up the cutis) and subcutaneous tissues, that primarily consists of dense irregular connective tissue and cushions the body from stress and strain. It is divided in ...
, particularly around blood vessels, as well as in the mucosa of the mouth,
foreskin In male human anatomy, the foreskin, also known as the prepuce, is the double-layered fold of skin, mucosal and muscular tissue at the distal end of the human penis that covers the glans and the urinary meatus. The foreskin is attached to the gl ...
, and
vaginal epithelium The vaginal epithelium is the inner lining of the vagina consisting of multiple layers of (squamous) cells. The basal membrane provides the support for the first layer of the epithelium-the basal layer. The intermediate layers lie upon the basal ...
. They can be found in other tissues, such as
lymph node A lymph node, or lymph gland, is a kidney-shaped organ of the lymphatic system and the adaptive immune system. A large number of lymph nodes are linked throughout the body by the lymphatic vessels. They are major sites of lymphocytes that includ ...
s, particularly in association with the condition
Langerhans cell histiocytosis Langerhans cell histiocytosis (LCH) is an abnormal clonal proliferation of Langerhans cells, abnormal cells deriving from bone marrow and capable of migrating from skin to lymph nodes. Symptoms range from isolated bone lesions to multisystem di ...
(LCH).


Function

In
skin Skin is the layer of usually soft, flexible outer tissue covering the body of a vertebrate animal, with three main functions: protection, regulation, and sensation. Other animal coverings, such as the arthropod exoskeleton, have different de ...
infection An infection is the invasion of tissues by pathogens, their multiplication, and the reaction of host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmissible disease or communicable dis ...
s, the local Langerhans cells take up and process
microbial A microorganism, or microbe,, ''mikros'', "small") and ''organism'' from the el, ὀργανισμός, ''organismós'', "organism"). It is usually written as a single word but is sometimes hyphenated (''micro-organism''), especially in olde ...
antigen In immunology, an antigen (Ag) is a molecule or molecular structure or any foreign particulate matter or a pollen grain that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response. ...
s to become fully functional
antigen-presenting cell An antigen-presenting cell (APC) or accessory cell is a cell that displays antigen bound by major histocompatibility complex (MHC) proteins on its surface; this process is known as antigen presentation. T cells may recognize these complexes using ...
s. Generally, tissue-resident macrophages are involved in immune homeostasis and the uptake of apoptotic bodies. However, Langerhans cells can also take on a
dendritic cell Dendritic cells (DCs) are antigen-presenting cells (also known as ''accessory cells'') of the mammalian immune system. Their main function is to process antigen material and present it on the cell surface to the T cells of the immune system. The ...
-like phenotype and migrate to
lymph node A lymph node, or lymph gland, is a kidney-shaped organ of the lymphatic system and the adaptive immune system. A large number of lymph nodes are linked throughout the body by the lymphatic vessels. They are major sites of lymphocytes that includ ...
s to interact with
naive T-cell In immunology, a naive T cell (Th0 cell) is a T cell that has differentiated in the thymus, and successfully undergone the positive and negative processes of central selection in the thymus. Among these are the naive forms of helper T cells (CD4 ...
s. Langerhans cells derive from primitive erythro-myeloid progenitors that arise in the yolk sac outside the
embryo An embryo is an initial stage of development of a multicellular organism. In organisms that reproduce sexually, embryonic development is the part of the life cycle that begins just after fertilization of the female egg cell by the male sperm c ...
in the first trimester of pregnancy, and under normal circumstances persist throughout life, being replenished by local proliferation as necessary. If the skin becomes severely inflamed, perhaps because of infection, blood monocytes are recruited to the affected region and differentiate into replacement LCs.
Langerin Langerin (CD207) is a type II transmembrane protein which is encoded by the ''CD207'' gene in humans. It was discovered by scientists Sem Saeland and Jenny Valladeau as a main part of Birbeck granules. Langerin is C-type lectin receptor on Lang ...
is a protein found in Langerhans cells, and
dendritic cells Dendritic cells (DCs) are antigen-presenting cells (also known as ''accessory cells'') of the mammalian immune system. Their main function is to process antigen material and present it on the cell surface to the T cells of the immune system. The ...
.


Clinical significance


Langerhans cell histiocytosis

In the
rare disease A rare disease is any disease that affects a small percentage of the population. In some parts of the world, an orphan disease is a rare disease whose rarity means there is a lack of a market large enough to gain support and resources for discove ...
Langerhans cell histiocytosis Langerhans cell histiocytosis (LCH) is an abnormal clonal proliferation of Langerhans cells, abnormal cells deriving from bone marrow and capable of migrating from skin to lymph nodes. Symptoms range from isolated bone lesions to multisystem di ...
(LCH), an excess of cells similar to these cells are produced. However LCH cells stain positive to
CD14 CD14 (cluster of differentiation 14) is a human protein made mostly by macrophages as part of the innate immune system. It helps to detect bacteria in the body by binding lipopolysaccharide (LPS), a pathogen-associated molecular pattern (PAMP). C ...
which is a monocyte marker and shows a different, hematopoietic origin for the disorder. LCH can cause damage to
skin Skin is the layer of usually soft, flexible outer tissue covering the body of a vertebrate animal, with three main functions: protection, regulation, and sensation. Other animal coverings, such as the arthropod exoskeleton, have different de ...
, bone and other organs.


HIV

Langerhans cells may be initial cellular targets in the sexual transmission of HIV, and may be a target, reservoir, and vector of dissemination. Langerhans cells have been observed in foreskin, vaginal, and oral mucosa of humans; the lower concentrations in oral mucosa suggest that it is not a likely source of
HIV The human immunodeficiency viruses (HIV) are two species of ''Lentivirus'' (a subgroup of retrovirus) that infect humans. Over time, they cause acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of the immune ...
infection relative to foreskin and vaginal mucosa.


Human papillomavirus

High-risk
human papillomavirus Human papillomavirus infection (HPV infection) is caused by a DNA virus from the ''Papillomaviridae'' family. Many HPV infections cause no symptoms and 90% resolve spontaneously within two years. In some cases, an HPV infection persists and res ...
es (HPV) are sexually transmitted viruses causally associated with several cancers including cervical, vaginal, anal, and head and neck cancers that cause significant morbidity and mortality worldwide. Over half of all
cervical cancer Cervical cancer is a cancer arising from the cervix. It is due to the abnormal growth of cells that have the ability to invade or spread to other parts of the body. Early on, typically no symptoms are seen. Later symptoms may include abnormal va ...
cases are associated with HPV16, the most common of the cancer-causing high-risk genotypes. During its natural life cycle, HPV16 infects the basal cells of the epithelium and interacts with Langerhans cells within the epithelial layer, which are responsible for initiating immune responses against epithelial invading pathogens. However, HPV does not activate Langerhans cells ''in vitro'', and this may represent a key mechanism by which HPV evades immune detection ''in vivo''. Specifically, HPV16 entry into Langerhans cells via the
annexin A2 Annexin A2 also known as annexin II is a protein that in humans is encoded by the ''ANXA2'' gene. Annexin 2 is involved in diverse cellular processes such as cell motility (especially that of the epithelial cells), linkage of membrane-associated ...
/
S100A10 S100 calcium-binding protein A10 (S100A10), also known as p11, is a protein that is encoded by the ''S100A10'' gene in humans and the ''S100a10'' gene in other species. S100A10 is a member of the S100 family of proteins containing two EF-hand ca ...
heterotetramer results in suppressive signaling and lack of Langerhans cell-mediated immune responses. This Langerhans cell-targeted immune escape mechanism seems to be conserved among different HPV genotypes enabling these viruses to remain undetected in the absence of other inflammatory events. T cells exposed to these inactivated Langerhans cells are not anergic, and can be activated against HPV upon receiving the appropriate stimuli at a later time point. It was demonstrated that Langerhans cells in HPV-induced cervical lesions were spherical, lacked dendrites, and secreted the suppressive cytokine IL-10 ''in vivo''. The authors further demonstrated that the number of IL-10 secreting immunosuppressive Langerhans cells, and the amount of IL-10 produced in lesions, corresponded with the severity of histopathology and HPV viral load, providing evidence of an active immunosuppressive mechanism employed by HPV that targets Langerhans cells ''in vivo''.


Dengue fever

Langerhans cells are also the initial target of the virus that causes
dengue fever Dengue fever is a mosquito-borne tropical disease caused by the dengue virus. Symptoms typically begin three to fourteen days after infection. These may include a high fever, headache, vomiting, muscle and joint pains, and a characteristic ...
during its development.


Declining function during ageing

During ageing the capacity of Langerhans cells to migrate declines. This compromises immunity and exposes the skin to infectious diseases and cancer.


History

Langerhans cells are named after
Paul Langerhans Paul Langerhans (25 July 1847 – 20 July 1888) was a German pathologist, physiologist and biologist, credited with the discovery of the cells that secrete insulin, named after him as the islets of Langerhans. Eponymous terms * Islets of Langer ...
, a
German German(s) may refer to: * Germany (of or related to) **Germania (historical use) * Germans, citizens of Germany, people of German ancestry, or native speakers of the German language ** For citizens of Germany, see also German nationality law **Ge ...
physician A physician (American English), medical practitioner ( Commonwealth English), medical doctor, or simply doctor, is a health professional who practices medicine, which is concerned with promoting, maintaining or restoring health through t ...
and
anatomist Anatomy () is the branch of biology concerned with the study of the structure of organisms and their parts. Anatomy is a branch of natural science that deals with the structural organization of living things. It is an old science, having it ...
, who discovered the cells at the age of 21 while he was a
medical student A medical school is a tertiary educational institution, or part of such an institution, that teaches medicine, and awards a professional degree for physicians. Such medical degrees include the Bachelor of Medicine, Bachelor of Surgery (MBBS, MB ...
. Because of their
dendrite Dendrites (from Greek δένδρον ''déndron'', "tree"), also dendrons, are branched protoplasmic extensions of a nerve cell that propagate the electrochemical stimulation received from other neural cells to the cell body, or soma, of the n ...
-like appearance, he mistakenly identified the cells as part of the
nervous system In biology, the nervous system is the highly complex part of an animal that coordinates its actions and sensory information by transmitting signals to and from different parts of its body. The nervous system detects environmental changes t ...
.


See also

*
Langhans giant cell Langhans giant cells are large cells found in granulomatous conditions. They are formed by the fusion of epithelioid cells (macrophages), and contain nuclei arranged in a horseshoe-shaped pattern in the cell periphery. Although traditionall ...


References


External links

* * * * {{Blood Mononuclear phagocytes Skin anatomy Epithelial cells