Chemokine (C-C motif) ligand 20 (CCL20) or liver activation regulated chemokine (LARC) or Macrophage Inflammatory Protein-3 (MIP3A) is a small
cytokine belonging to the CC
chemokine family. It is strongly
chemotactic for
lymphocytes and weakly attracts
neutrophils.
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 intercellula ...
s surrounding these tissues. CCL20 elicits its effects on its target cells by binding and activating the
chemokine receptor 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 ...
.
expression of CCL20 can be induced by
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 ...
factors such as
lipopolysaccharide (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 inclu ...
s,
liver,
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
The lungs are the primary organs of the respiratory system in humans and most other animals, including some snails and a small number of fish. In mammals and most other vertebrates, two lungs are located near the backbone on either side of t ...
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 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