CXCL10

Official Full Name

C-X-C motif chemokine ligand 10

Organism

Homo sapiens

GeneID

3627

Background

This antimicrobial gene encodes a chemokine of the CXC subfamily and ligand for the receptor CXCR3. Binding of this protein to CXCR3 results in pleiotropic effects, including stimulation of monocytes, natural killer and T-cell migration, and modulation of adhesion molecule expression. This gene may also be a key regulator of the 'cytokine storm' immune response to SARS-CoV-2 infection. [provided by RefSeq, Sep 2020]

Synonyms

C7; IFI10; INP10; IP-10; crg-2; mob-1; SCYB10; gIP-10;

Bio Chemical Class

Cytokine: CXC chemokine

Protein Sequence

MNQTAILICCLIFLTLSGIQGVPLSRTVRCTCISISNQPVNPRSLEKLEIIPASQFCPRVEIIATMKKKGEKRCLNPESKAIKNLLKAVSKERSKRSP

Open

Disease

Crohn disease, Diabetes mellitus, Immune system disease, Indeterminate colitis, Solid tumour/cancer, Ulcerative colitis

Approved Drug

Clinical Trial Drug

6 +

Discontinued Drug

Cat.No.	Product Name	Price

Cat.No.	Product Name	Price

Cat.No.	Product Name	Price

Cat.No.	Product Name	Tag	Price

Cat.No.	Product Name	Price

Detailed Information

The CXCL10 gene was first discovered by Luster in 1985 while treating a cancer cell line (U937) with synthetic IFN-γ. The gene's cDNA has an open reading frame of 1173 base pairs and 4 exons, which makes a protein that has 98 amino acids and weighs 10 kDa. The main result of the CXCL10 gene is a protein that weighs 12 kDa and has two disulfide bridges inside it. These bridges are important for keeping the protein stable and working properly. After signal peptidase degradation, a 10 kDa released polypeptide is made with four conserved cysteine residues at the N-terminus, playing key roles in the formation of the protein's tertiary structure. The CXCL10 gene is found on chromosome 4 in the q21 area and is related to a type of leukemia called acute monocytic/B lymphocytic leukemia, which involves a specific change in the chromosome known as a translocation between chromosomes 4 and 11. Human CXCL10 and mouse CXCL10 have 63% similarity in their cDNA sequences, showing that the gene has been largely preserved throughout evolution.

Molecular Mechanism and Receptor Interaction

Also known as gamma interferon-induced protein 10 (IP-10), CXCL10 is a member of the CXC chemokine family. This chemokine is made by different types of cells, such as monocytes, blood vessel cells, fibroblasts, white blood cells, neutrophils, eosinophils, skin cells, and supporting tissue cells. It is mostly released when cells are stimulated by IFN-γ. CXCL10 works by attaching to its receptor, CXCR3, which is a protein found on the surface of certain immune cells like active T cells, B cells, NK cells, dendritic cells, and macrophages. The production of CXCL10 mainly relies on the end part of CXCR3, which is important for the uptake of CXCR3, movement towards chemical signals, and calcium release. Interestingly, CXCR3 shows three splice variants: CXCR3-A, CXCR3-B, and CXCR3-alt, with changes in expression across cell types leading to varying growth effects upon CXCL10 binding.

Complex Signaling Pathways Network

CXCL10 works by starting several communication pathways to carry out its biological tasks. In human lung epithelial cells, the p38/MAPK and PI3K pathways play important roles in CXCL10/CXCR3-mediated chemotaxis. The main CXCR3-A type triggers certain signaling pathways in the cell through a specific connection (Gαi coupling). This leads to an increase in calcium inside the cell, which promotes DNA production, cell growth, and movement of cells. On the other hand, CXCR3-B works with Gαs, which activates adenylate cyclase. This process helps to stop the growth and movement of vascular cells. During viral diseases like rabies, CXCL10 is produced in macrophages by activating the ERK1/2 pathway. In brain cells called microglia, it is produced through the p38 and NF-κB pathways.

Extensive Immunoregulatory Functions

CXCL10 has many important roles in controlling the immune system. It chemotactically leads CXCR3-positive cells, including macrophages (microglia in the CNS), dendritic cells, NK cells, and activated T lymphocytes (CD4+ Th cells, CD8+ Tc cells), to sites of inflammation, infection, and tumors through its "homing" function. CXCL10 mainly affects how Th1 cells work among T cell types. Th1 cells make substances called cytokines, such as IL-2, IFN-γ, and lymphotoxin-α. These help activate macrophages, improve their ability to target threats, and enhance cell-killing functions. IFN-γ made by Th1 cells causes other cells to make CXCL10. In turn, CXCL10 helps bring Th1 cells to the area, creating a cycle that is important in the development of several conditions.

Figure 1 shows that p38, JNK, ERK, Akt, and NFκB pathways, along with STAT1, induce CXCL10 transcription in response to various stimuli in human cells. Figure 1. The p38, JNK, ERK, Akt, and NFκB pathways, along with STAT1, induce CXCL10 transcription in response to various stimuli in human cells. (Liu M, et al., 2011)

Disease Regulation and Clinical Application Prospects

The amounts of CXCL10 can change a lot in different diseases, making it important for diagnosis and treatment. In viral diseases, CXCL10 plays a role in several viruses, such as SARS coronavirus, HIV, hepatitis B and C viruses, Ebola virus, and dengue virus. In HIV patients, high amounts of CXCL10 over time are linked to unsuccessful outcomes in immunotherapy after starting strong antiviral treatment. In people with both HCV and HIV, higher amounts of CXCL10 are linked to more serious liver damage. In bacterial illnesses, CXCL10 is a proven immunodiagnostic sign for diseases like TB. In viral infections, CXCL10 helps indicate how severe the disease is, especially in brain malaria. It influences the outcome by influencing the movement and activity of CD8+ T cells. These results help in creating new ways to diagnose and treat issues related to CXCL10.

References:

Reschke R, Gajewski TF. CXCL9 and CXCL10 bring the heat to tumors. Sci Immunol. 2022 Jul 22;7(73):eabq6509.
Qiao X, Zhang W, et al. Role of CXCL10 in Spinal Cord Injury. Int J Med Sci. 2022 Nov 14;19(14):2058-2070.
Liu M, Guo S, et al. CXCL10/IP-10 in infectious diseases pathogenesis and potential therapeutic implications. Cytokine Growth Factor Rev. 2011 Jun;22(3):121-30.

Quick Inquiry

Interested in learning more?

Contact us today for a free consultation with the scientific team and discover how Creative Biogene can be a valuable resource and partner for your organization.

Request a quote today!

Inquiry