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il10

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Official Full Name
interleukin 10
Background
factor involved in the inhibition of cytokine synthesis [RGD, Feb 2006]
Synonyms
IL10; interleukin 10; IL10X; interleukin-10; CSIF; IL-10; cytokine synthesis inhibitory factor; IL 10; IL10A; T cell growth inhibitory factor; TGIF; T-cell growth inhibitory factor; GVHDS; MGC126450; MGC126451; zgc:194510; zgc:194518

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:

  1. Kumar S, et al. Interleukin-10: A Compelling Therapeutic Target in Patients with Irritable Bowel Syndrome. Clinical Therapeutics, 2017, 39(3):632.
  2. 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.
  3. 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.
  4. 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.
  5. 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.