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Chemokine (C-X-C motif) ligand 16 (CXCL16) is a small cytokine belonging to the CXC chemokine family. Larger than other chemokines (with 254 amino acids), CXCL16 is composed of a CXC chemokine domain, a mucin-like stalk, a transmembrane domain and a cytoplasmic tail containing a potential tyrosine phosphorylation site that may bind SH2.

These are unusual features for a chemokine, and allow CXCL16 to be expressed as a cell surface bound molecule, as well as a soluble chemokine. CXCL16 is produced by dendritic cells found in the T cell zones of lymphoid organs, and by cells found in the red pulp of the spleen. Cells that bind and migrate in response to CXCL16 include several subsets of T cells, and natural killer T (NKT) cells.

CXCL16 interacts with the chemokine receptor CXCR6, also known as Bonzo. Expression of CXCL16 is induced by the inflammatory cytokines IFN-gamma and TNF-alpha. The gene for human CXCL16 is located on chromosome 17.

The administration of folinic acid, which forces the methylation of CXCL 16, induces high levels of methylation of the CXCL 16 gene promoter in colon, ileum and lung and causes iNKT cells accumulation in these tissues. Colonization of neonatal GF mice, but not in adult mice, with a conventional microbiota decreases hypermethylation levels of CXCL 16.

References

1. ^ Matloubian M, David A, Engel S, Ryan J, Cyster J (2000). "A transmembrane CXC chemokine is a ligand for HIV-coreceptor Bonzo". Nat Immunol. 1 (4): 298–304. doi:10.1038/79738. PMID 11017100. S2CID 22773861.
2. ^ Abel S, Hundhausen C, Mentlein R, Schulte A, Berkhout T, Broadway N, Hartmann D, Sedlacek R, Dietrich S, Muetze B, Schuster B, Kallen K, Saftig P, Rose-John S, Ludwig A (2004). "The transmembrane CXC-chemokine ligand 16 is induced by IFN-gamma and TNF-alpha and shed by the activity of the disintegrin-like metalloproteinase ADAM10". J Immunol. 172 (10): 6362–72. doi:10.4049/jimmunol.172.10.6362. PMID 15128827.
3. Wilbanks A, Zondlo S, Murphy K, Mak S, Soler D, Langdon P, Andrew D, Wu L, Briskin M (2001). "Expression cloning of the STRL33/BONZO/TYMSTRligand reveals elements of CC, CXC, and CX3C chemokines". J Immunol. 166 (8): 5145–54. doi:10.4049/jimmunol.166.8.5145. PMID 11290797.
4. Olszak T, An D, Zeissig S, Vera MP, Richter J, Franke A, Glickman JN, Siebert R, Baron RM, Kasper DL, Blumberg RS (2012). "Microbial exposure during early life has persistent effects on natural killer T cell function". Science. 336 (6080): 489–493. Bibcode:2012Sci...336..489O. doi:10.1126/science.1219328. PMC 3437652. PMID 22442383.

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