Chemokine (C-C motif) ligand 20 (CCL20) or liver activation regulated chemokine (LARC) or Macrophage Inflammatory Protein-3 (MIP3A) is a small
cytokine
Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in a ...
belonging to the CC
chemokine
Chemokines (), or chemotactic cytokines, are a family of small cytokines or Cell signaling, signaling proteins secreted by Cell (biology), cells that induce directional movement of leukocytes, as well as other cell types, including endothelial a ...
family. It is strongly
chemotactic for
lymphocytes and weakly attracts
neutrophil
Neutrophils (also known as neutrocytes or heterophils) are the most abundant type of granulocytes and make up 40% to 70% of all white blood cells in humans. They form an essential part of the innate immune system, with their functions varying in ...
s.
CCL20 is implicated in the formation and function of
mucosal lymphoid tissues via chemoattraction of
lymphocytes and
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. ...
s towards the
epithelial cell
Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercell ...
s surrounding these tissues. CCL20 elicits its effects on its target cells by binding and activating the
chemokine receptor
Chemokine receptors are cytokine receptors found on the surface of certain cells that interact with a type of cytokine called a chemokine. There have been 20 distinct chemokine receptors discovered in humans. Each has a rhodopsin-like 7- tr ...
CCR6
Chemokine receptor 6 also known as CCR6 is a CC chemokine receptor protein which in humans is encoded by the ''CCR6'' gene. CCR6 has also recently been designated CD196 ( cluster of differentiation 196). The gene is located on the long arm of ...
.
Gene
In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...
expression of CCL20 can be induced by
microbial factors such as
lipopolysaccharide
Lipopolysaccharides (LPS) are large molecules consisting of a lipid and a polysaccharide that are bacterial toxins. They are composed of an O-antigen, an outer core, and an inner core all joined by a covalent bond, and are found in the outer ...
(LPS), and inflammatory cytokines such as
tumor necrosis factor and
interferon-γ, and down-regulated by
IL-10.
CCL20 is expressed in several tissues with highest expression observed in peripheral blood
lymphocytes,
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 inc ...
s,
liver
The liver is a major organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the synthesis of proteins and biochemicals necessary for digestion and growth. In humans, it ...
,
appendix
Appendix, or its plural form appendices, may refer to:
__NOTOC__ In documents
* Addendum, an addition made to a document by its author after its initial printing or publication
* Bibliography, a systematic list of books and other works
* Index (pub ...
, and
fetal lung and lower levels in thymus, testis, prostate and gut.
The gene for CCL20 (''scya20'') is located on chromosome 2 in humans.
Recent research
[Regional Neural Activation Defines a Gateway for Autoreactive T Cells to Cross the Blood-Brain Barrier , author = Arima, Yasunobu; Harada, Masaya; Kamimura, Daisuke; Park, Jin-Haeng; Kawano, Fuminori; Yull, Fiona E.; Kawamoto, Tadafumi; Iwakura, Yoichiro; Betz, Ulrich A.K.; Marquez, Gabriel; Blackwell, Timothy S.; Ohira, Yoshinobu; Hirano, Toshio; Murakami, Masaaki , Cell doi:10.1016/j.cell.2012.01.022 (volume 148 issue 3 pp.447 - 457)] in an animal model of multiple sclerosis known as experimental autoimmune encephalitis (EAE) demonstrated that regional neural activation can create "gates" for pathogenic
CD4
In molecular biology, CD4 (cluster of differentiation 4) is a glycoprotein that serves as a co-receptor for the T-cell receptor (TCR). CD4 is found on the surface of immune cells such as T helper cells, monocytes, macrophages, and dendritic ...
+ T cells to enter the CNS by increasing CCL20 expression, especially at L5. Sensory nerve stimulation, elicited by using muscles in the leg or electrical stimulation as in Arima et al., 2012, activates sympathetic neurons whose axons run through the dorsal root ganglia containing cell bodies of the stimulated afferent sensory nerve. Sympathetic neuronal activity activates IL-6 amplifier resulting in increased regional CCL20 expression and subsequent pathogenic CD4+ T cell accumulation at the same spinal cord level. CCL20 expression was observed to be dependent on IL-6 amplifier activation, which is dependent on
NF-κB
Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) is a protein complex that controls transcription of DNA, cytokine production and cell survival. NF-κB is found in almost all animal cell types and is involved in cellular ...
and
STAT3 activation. This research provides evidence for a critical role for CCL20 in autoimmune pathogenesis of the central nervous system.
References
Further reading
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External links
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{{Chemokine receptor modulators
Cytokines