Cxcl10

What is CXCL10 protein?

CXCL10 (C-X-C motif chemokine ligand 10) gene is a protein coding gene which situated on the long arm of chromosome 4 at locus 4q21. 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. The CXCL10 protein is consisted of 98 amino acids and its molecular mass is approximately 10.9 kDa.

What is the function of CXCL10 protein?

CXCL10 protein is an important cytokine with many biological functions. First, it can act as a chemokine to attract and activate immune cells, such as T cells and natural killer cells, promoting their movement to the site of inflammation and participating in the regulation of inflammatory response. Secondly, CXCL10 can induce endothelial cell proliferation and migration, promote angiogenesis, and thus play a role in tissue repair and regeneration. In addition, CXCL10 also has anti-tumor activity, which can inhibit the growth and spread of tumor cells.

Fig1. Schematic of the signaling pathways involved in TNF-α augments CXCL10/CXCR3 axis to promote CC cell EMT, invasion and migration. (Zhengcheng Wang, 2021)

CXCL10 Related Signaling Pathway

CXCL10 protein is an important cytokine belonging to the C-X-C family. It is mainly involved in a variety of signaling pathways, the most important of which is the inflammatory response signaling pathway. CXCL10 can bind to its receptor CXCR3, activate downstream signaling pathways, and trigger chemotaxis and activation of inflammatory cells, such as T cells, natural killer cells and monocytes. In addition, CXCL10 is involved in biological processes such as angiogenesis, tumor metastasis, and neurodevelopment.

CXCL10 Related Diseases

The CXCL10 protein has been implicated in a variety of diseases, including infectious diseases, autoimmune diseases, and tumors. In infectious diseases, CXCL10 is involved in the migration of chemotactic immune cells to the site of infection and in regulating the inflammatory response. In autoimmune diseases, CXCL10 can cause autoimmune responses and tissue damage. In tumors, CXCL10 can promote tumor cell growth, invasion and metastasis.

Bioapplications of CXCL10

In terms of clinical diagnosis, levels of CXCL10 have been used to assess the activity of certain inflammatory diseases, such as rheumatoid arthritis (RA). In addition, CXCL10 mRNA release assay (IP-10.TB) has been developed as a novel Mycobacterium tuberculosis specific assay for the diagnosis of mycobacterium tuberculosis infection, showing diagnostic sensitivity and specificity comparable to the existing T-SPOT.TB assay. In particular, there is a higher positive detection rate in patients co-infected with HIV, which provides a new tool for screening and preventive treatment of tuberculosis infection in people with immune abnormalities.

Case Study 1: Tadaatsu Imaizumi, 2021

Various viruses including a novel coronavirus (SARS-CoV-2) can infect the kidney. When viruses invade the glomeruli from the bloodstream, glomerular endothelial cells (GECs) initiate the innate immune reactions. Role of IFIT1/2/3 in the expression of C-X-C motif chemokine ligand 10 (CXCL10) was also examined. Human GECs were cultured and stimulated with polyinosinic-polycytidylic acid (poly IC), a synthetic TLR3 agonist. Real-time qPCR, Western blotting, and ELISA were used to examine the expression of IFIT1/2/3, IFN-β, and CXCL10. RNA interference against IFN-β or IFIT1/2/3 was also performed. xpression of IFIT1/2/3 and CXCL10 was induced by poly IC in GECs. Knockdown of IFIT1/2/3 decreased the CXCL10 expression. Knockdown of IFIT3 decreased the expression of IFIT1 and IFIT2 proteins.

Fig1. CXCL10 concentration in the medium was measured using an ELISA kit.

Fig2. The expression of mRNA and protein for IFIT1, IFIT2, IFIT3, and CXCL10 was analyzed using qRT-PCR.

Case Study 2: Michelle Silasi, 2020

The process of implantation, trophoblast invasion and placentation demand continuous adaptation and modifications between the trophoblast (embryonic) and the decidua (maternal). Human chorionic gonadotropin (hCG) is one of the earliest hormones produced by the blastocyst and has potent immune modulatory effects, especially in relation to T cells. This study hypothesized that trophoblast-derived hCG modulates the immune population present at the maternal fetal interface by modifying the cytokine profile produced by the stromal/decidual cells. Using in vitro models from decidual samples the researchers demonstrate that hCG inhibits CXCL10 expression by inducing H3K27me3 histone methylation, which binds to Region 4 of the CXCL10 promoter, thereby suppressing its expression. hCG-induced histone methylation is mediated through EZH2, a functional member of the PRC2 complex. Regulation of CXCL10 expression has a major impact on the capacity of endometrial stromal cells to recruit CD8 cells. Alterations in this immune regulatory function, such as during infection, will have detrimental effects on the success of the pregnancy.

Fig3. Quantification of CXCL10 protein expression in HESC treated with cAMP or decidualized with estrogen, progesterone and cAMP.

Fig4. Human term decidua tissues were treated with LPS (100 ng/ml) for 24 followed by evaluation of CXCL10 protein expression by Luminex.

Cxcl10 has several biochemical functions, for example, CXCR3 chemokine receptor binding,cAMP-dependent protein kinase regulator activity,chemokine activity. Some of the functions are cooperated with other proteins, some of the functions could acted by Cxcl10 itself. We selected most functions Cxcl10 had, and list some proteins which have the same functions with Cxcl10. You can find most of the proteins on our site.

Cxcl10 has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with Cxcl10 here. Most of them are supplied by our site. Hope this information will be useful for your research of Cxcl10.

DPP4;DPP8