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Daniel J. Catron and Albert Zlotnik: Structure
Daniel J. Catron and Albert Zlotnik: Structure
Daniel J. Catron and Albert Zlotnik: Structure
Chromosome location
Alternative names
Mouse CCL28 maps to a distal region of chromo-
CCL28 is the systematic ligand nomenclature as some 13 according to interspecific backcross analysis.
described by Zlotnik and Yoshie (2000) while This region is syntenic with human chromosome 5q.
As such, human CCL28 is the first chemokine to map Discussion of crystal structure
to chromosome 5.
No structural studies have been reported.
Cells and tissues that express the
gene Important homologies
Northern blotting indicates human CCL28 is pre- The CC chemokines with the greatest degree of
dominantly expressed in prostate, colon, spleen, and to homology to CCL28 are CCL27/CTACK, CCL25/
a lesser degree by peripheral blood leukocytes. Mouse TECK, CCL17/TARC, CCL20/MIP-3, and
CCL28 is predominantly expressed in testes and less CCL19/MIP-3.
so in the kidney and brain. Using real time
quantitative PCR (TaqMan2 ), human CCL28 is
shown to be expressed in lymphoid and hematopoietic
libraries. Human and mouse CCL28 is most highly Posttranslational modifications
expressed by normal and pathological cells of the
colon. TaqMan assays also showed mouse CCL28 to While CCL28 is glycosylated in its native form,
be highly expressed in mesenteric lymph nodes, Peyer's it is unknown if this affects the activity of the
patches, and stomach cells. Immunohistochemical protein.
staining suggests that epithelial cells produce CCL28.
RECEPTOR UTILIZATION
Sequence
The CCL28 receptor has been identified as the former
See Figure 1. orphan receptor GPR2, now called CCR10. Real-
time, quantitative PCR (TaqMan2 ) was used to
determine expression levels in various cDNA libraries
Description of protein derived from various human organs and cell types.
CCR10 is expressed in dermal microvascular
Both human and mouse CCL28 contain six cysteines. endothelial cells, dermal fibroblasts, melanocytes,
There are two cysteine residues in addition to the four T cells, and skin-derived Langerhans cells. In organs,
conserved ones normally found in CC chemokines. It CCR10 is most highly expressed in the small intestine
is hypothesized that the additional disulfide bond and colon and to a lesser degree in fetal liver, fetal
might confine the extended C-terminal tail to the lung, fetal spleen, fetal testes, fetal brain, and uterus,
body of the chemokine. among others (Homey et al., 2000; Jarmin et al.,
Mouse CCL28:
MQQAGLTLMA VAVCVAFQTS EAILPMASSC CTEVSHHVSG RLLERVSSCS IQ
RADGDCDL AAVILHVKRR RICISPHNRT LKQWMRASEV KKNGRENVCS GKK
QPSRKDR KGHTTRKHRT RGTHRHEASR
Human CCL28:
MQQRGLAIVA LAVCAALHAS EAILPIASSC CTEVSHHISR RLLERVNMCR IQR
ADGDCDL AAVILHVKRR RICVSPHNHT VKQWMKVQAA KKNGKGNVCH RK
KHHGKRNS NRAHQGKHET YGHKTPY
CCL28 3
2000). CCR10 is also the receptor for CCL27. general by epithelial cells elsewhere including salivary
Calcium flux experiments show CCL28 is able to gland, trachea, and mammary epithelium.
specifically desensitize human and mouse CCR10-
transfectants to CCL27 (and vice versa) (Wang et al.,
2000). CCR10 is expressed in some T cell and B cell IN THERAPY
lines, but not in normal B cells. This suggests that
normal B cells may respond to CCL28 under certain
circumstances, but not in the resting state.
Preclinical ± How does it affect
disease models in animals?
IN VITRO ACTIVITIES No studies have been reported.
Bioassays used
References
Transwell chemotaxis assay.
Homey, B., Wang, W., Soto, H., Buchanan, M. E., Wiesenborn,
A., Catron, D., Muller, A., McClanahan, T. K., Dieu-Nosjean,
M. C., Orozco, R., Ruzicka, T., Lehmann, P., Oldham, E., and
IN VIVO BIOLOGICAL Zlotnik, A. (2000). Cutting edge: the orphan chemokine recep-
ACTIVITIES OF LIGANDS IN tor G protein-coupled receptor-2 (GPR-2, CCR10) binds the
skin-associated chemokine CCL27 (CCL27/ALP/ILC).
ANIMAL MODELS J. Immunol. 164, 3465±3470.
Jarmin, D. I., Rits, M., Bota, D., Gerard, N. P., Graham, G. J.,
Normal physiological roles Clark-Lewis, I., and Gerard, C. (2000). Cutting edge: identifica-
tion of the orphan receptor G-protein-coupled receptor 2 as
CCR10, a specific receptor for the chemokine ESkine.
Possibly chemoattracts resting CD4 and CD8 T cells J. Immunol. 164, 3460±3464.
and certain activated B cells. Pan, J., Kunkel, E. J., Gosslar, U., Lazarus, N. I., Langdon, P.,
Broadwell, K., Vierra, M. A., Genovese, M. C., Butcher, E. C.,
and Soler, D. (2000). A novel chemokine ligand for CCR10
and CCR3 expressed by epithelial cells in mucosal tissues.
Species differences J. Immunol. 165, 2943±2949.
Wang, W., Soto, H., Oldham, E. R., Buchanan, M. E., Homey, B.,
Because the human and mouse forms of CCL28 share Catron, D., Jenkins, N., Copeland, N. G., Gilbert, D. J.,
a high degree of homology and have comparable Nguyen, N., Abrams, J., Kershenovich, D., Smith, K.,
McClanahan, T., Vicari, A. P., and Zlotnik, A. (2000).
expression patterns, similar biological activities are Identification of a novel chemokine (CCL28), which binds to
expected. CCR10 (GPR2). J. Biol. Chem. 275, 22313±22323.
Zlotnik, A., and Yoshie, O. (2000). Chemokines: a new classifica-
tion system and their role in immunity. Immunity 12, 121±127.
PATHOPHYSIOLOGICAL ROLES
IN NORMAL HUMANS AND
DISEASE STATES AND
DIAGNOSTIC UTILITY
Normal levels and effects
Human and mouse CCL28 is highly expressed in
normal and pathological tissues of the colon and in