IL10

Official Full Name

interleukin 10

Organism

Homo sapiens

GeneID

3586

Background

The protein encoded by this gene is a cytokine produced primarily by monocytes and to a lesser extent by lymphocytes. This cytokine has pleiotropic effects in immunoregulation and inflammation. It down-regulates the expression of Th1 cytokines, MHC class II Ags, and costimulatory molecules on macrophages. It also enhances B cell survival, proliferation, and antibody production. This cytokine can block NF-kappa B activity, and is involved in the regulation of the JAK-STAT signaling pathway. Knockout studies in mice suggested the function of this cytokine as an essential immunoregulator in the intestinal tract. Mutations in this gene are associated with an increased susceptibility to HIV-1 infection and rheumatoid arthritis. [provided by RefSeq, May 2020]

Synonyms

CSIF; TGIF; GVHDS; IL-10; IL10A;

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Detailed Information

IL-10 is known as an-inflammatory cytokine and produced by various cells including immune cells like T and B cells, and tumor cell lines. Several reports have demonstrated that IL-10 is involved in many important physiological processes like the inhibition of antigen presentation and the release of proinflammatory cytokines, regulation of the proliferation and differentiation of several immune cell types.

IL-10 signaling

It has been shown that IL-10 serve as an anti-inflammatory cytokine via binding with IL-10 receptor, which is expressed on a variety of cells, particularly immune cells. Previous structure studies have shown that IL-10R is composed of 2 α chains and 2 β chains. Those two chains have distinct role that α binds with IL-10, and β works in signal transduction with access to IL-10. Studies have shown that binding of IL-10 to IL-10 receptor results in activation of kinase-1 and tyrosine kinase-2, which leads to phosphorylation of IL-10 receptor in turn. Phosphorylated IL-10R binds with signal transducer and activator of transcription (STAT)-3, resulting in phosphorylation of STAT3 by receptor-associated Janus activated kinases and the activation of downstream target genes such as the expression of suppressor of cytokine signaling (SOCS)-3 gene, which inhibits the production of proinflammatory cytokines and JAK/STAT-dependent signaling, and ultimately the expression of anti-inflammatory effectors. The whole signaling pathway is shown as Figure 1.

Figure 1. Signaling pathway of IL-10. (Kumar S, et al.)

Roles of IL-10 in related diseases

Accumulating evidences have demonstrated that IL-10 is implicated with various diseases including irritable bowel syndrome (IBS), obesity, Alzheimer’s disease (AD), cervical carcinoma and so on. Thus, it might be a potent anti-inflammatory biological therapy target for those diseases.

IL-10 and AD

Recently, some reports have considered that an imbalance between pro-inflammatory and anti-inflammatory cytokines may be an important phenomenon in AD. Thus, IL-10, an anti-inflammatory cytokine, must plays a crucial role in AD. Indeed, studies with transgenic AD mouse models have demonstrated that IL-10 significantly reduced neuroinflammation, enhanced neurogenesis and improved spatial cognitive dysfunction. Those findings indicated that IL-10 may have a positive function in neuroinflammation, cognitive dysfunction and neurodegeneration. Moreover, several studies also focus on the relationship between the functional polymorphisms of the IL-10 gene and AD, and conclude that the IL-10 polymorphisms are an additive and independent risk factor for AD.

IL-10 and cervical carcinoma

Studies have found that IL-10 production can be induced and maintained by various cells such as infected keratinocytes, some subsets of dendritic cells (DC) and tumor cells in the condition of HPV infection. Additionally, a number of data have shown that the HPV E2, E6 and E7 proteins act over IL-10 gene transcription, leading to the increasing of IL-10 levels, while IL-10 stimulates HPV E6 and E7 expression like Figure 2. Therefore, there is a vicious cycle between IL-10 and HPV, which might be contributed to the progression of a simple HPV infection to SIL or cervical cancer.

Figure 2. The interplay between IL-10 and HPV. (Berti F C, et al.)

In addition to the diseases mentioned above, IL-10 also has a complex regulation in others virus infection. A better understanding about IL-10 effects on the different physiological and pathological processes will be contributed to the further studies that IL-10 is function as a therapeutic target.

References:

Kumar S, et al. Interleukin-10: A Compelling Therapeutic Target in Patients with Irritable Bowel Syndrome. Clinical Therapeutics, 2017, 39(3):632.
Gotoh K, et al. Role of spleen-derived IL-10 in prevention of systemic low-grade inflammation by obesity [Review]. Endocrine Journal, 2017, 64(4):375.
Magalhães C A, et al. Alzheimer's disease and cytokine IL-10 gene polymorphisms: is there an association? Arq Neuropsiquiatr, 2017, 75(9):649-656.
Berti F C, et al. The role of interleukin 10 in human papilloma virus infection and progression to cervical carcinoma. Cytokine & Growth Factor Reviews, 2017, 34:1-13.
Rojas J M, et al. 1 IL-10: a multifunctional cytokine in viral infections. Journal of Immunology Research, 2017, (2017-02-20), 2017, 2017(4):6104054.

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