IL‑27 Recombinant Protein: Functional Analysis and Application of a Pleiotropic Cytokine in the Immune Regulatory Network

Author: Senior Product Manager of UA Views：12

This article focuses on the molecular characteristics and biological functions of interleukin‑27 (IL‑27). It systematically describes the pleiotropic effects of this IL‑6 family member in immune regulation through the IL‑27R/JAK‑STAT signaling pathway, analyzes the dual regulatory mechanisms of IL‑27 in anti‑tumor responses, obesity-associated inflammation and autoimmune diseases, and discusses its inhibitory effects during viral infection.

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IL-27 Recombinant Protein: Functional Analysis and Application of a Pleiotropic Cytokine in the Immune Regulatory Network

Brief Summary: Focusing on the molecular characteristics and biological functions of interleukin-27 (IL-27), this article systematically describes its pleiotropic roles in immune regulation as an IL-6 family member through the IL-27R/JAK-STAT signaling pathway, analyzes the bidirectional regulatory mechanisms of IL-27 in anti-tumor immunity, obesity-related inflammation, and autoimmune diseases, and discusses its inhibitory effects in viral infections.

I. Molecular Characteristics and Receptor System of IL-27.

IL-27 is a member of the IL-6 family and is structurally related to the IL-12 and IL-6 families. Its receptor IL-27R signals through the JAK/STAT signaling pathway. IL-27R is composed of IL-27Rα and the gp130 chain, where gp130 is also an important component of the receptors for cytokines such as IL-35, IL-6, and IL-11. Furthermore, gp130 and IL-27Rα can be expressed in cells including NIH3T3 cells, B cells, T cells, NK cells, DCs, monocytes, mast cells, endothelial cells, and adipocytes. This broad receptor distribution pattern determines the regulatory capacity of IL-27 across multiple immune and non-immune cell types. In healthy individuals, IL-27 can be produced by APCs such as DCs, macrophages, and monocytes through TLR- and IFN-γ-dependent mechanisms. IL-27 exhibits pleiotropic effects in tumors, autoimmunity, and obesity-related inflammation.

II. Bidirectional Regulatory Role of IL-27 in Tumor Immunity.

IL-27 exhibits complex dual regulatory roles in tumor immunity, possessing both anti-tumor and pro-tumor potential. In terms of anti-tumor effects, reported mechanisms include: inducing IFN-γ production and enhancing the survival and differentiation capacity of tumor-specific CD8+ T cells; activating T cell- and NK cell-mediated anti-tumor immune responses; promoting hematopoietic stem cell expansion and differentiation into M1 phenotype myeloid progenitors; mediating CD8+ T cell immune responses; inducing apoptosis of malignant B cells; activating NK cells to induce tumor cell apoptosis through Fas/FasL-dependent mechanisms; combined with polyinosinic-polycytidylic acid to induce tumor cell apoptosis by enhancing TLR3 expression; inhibiting tumor tissue neovascularization by inducing CXCL10 and IFN-γ-induced monokine production; and impeding tumor neovascularization by downregulating pro-angiogenic genes and upregulating anti-angiogenic genes.

In terms of pro-tumor effects, IL-27 can activate NFIL3 and T-bet to induce TIM-3 expression; activate STAT1 to drive Treg expression of CD39, thereby exerting Treg pro-tumor effects; and activate STAT1 to mediate PD-L1 expression. IL-27 has been used to predict breast cancer survival, immune checkpoint expression, and immune cell infiltration. Combining PD-1/PD-L1 or IDO blockade may be a better strategy. These studies indicate that the role of IL-27 in tumor immunity is context-dependent, with its functional direction determined by tumor type, immune microenvironment status, and IL-27 concentration levels.

III. Dual Role of IL-27 in Obesity and Metabolic Regulation.

Theoretically, IL-27/IL-27Rα signaling can resist the development of obesity and insulin resistance, promoting thermogenesis and energy expenditure. In practice, however, IL-27 has dual roles in regulating inflammatory responses within adipocytes. In in vitro cell experiments, it was detected that both preadipocytes and adipocytes can secrete IL-27 under TNF-α or LPS stimulation.

In terms of inhibiting obesity development, IL-27 specifically regulates the number of Tregs in mouse visceral adipose tissue through WSX-1 signaling, thereby inhibiting obesity development. In the absence of inflammatory factor intervention, IL-27 stimulation of preadipocytes reduces the mRNA expression of classic inflammatory genes such as MCP-1, IL-6, TNF-α, and COX-2 through activation of ERK and JNK/STAT3 pathways, suppressing inflammatory responses. Additionally, IL-27 acts directly on adipocytes, inducing thermogenic effects on UCP1 expression through the p38MAPK/PGC-1α signaling pathway, promoting thermogenesis and thereby regulating obesity.

In terms of promoting obesity development, when obesity has already induced inflammation, IL-27 exacerbates the progression of inflammation within adipose tissue. In HFD-fed IL-27Rα knockout mouse models, IL-6 and TNF-α are increased in adipose tissue, along with increased macrophage infiltration. In in vitro experiments, after adding TNF-α to the culture medium, IL-27 can synergize with TNF-α to significantly increase the expression of MCP-1, IL-6, COX-2, and TNF-α. Meanwhile, the effects of IL-27 also differ between adults and children. Studies have shown that serum IL-27 levels in adults decrease with increasing obesity severity, and IL-27 levels return to normal after successful weight loss. However, elevated IL-27 levels are observed in the plasma of obese children.

IV. Regulatory Mechanisms of IL-27 in Autoimmune Diseases.

Taking rheumatoid arthritis as an example, IL-27 exhibits both anti-inflammatory and pathogenic properties. In terms of inhibiting pro-inflammatory cytokine secretion, in the early stages of RA, IL-27 may delay RA progression by inhibiting the secretion of IL-17 and IL-6. IL-27 can naturally antagonize IL-6 by competing with IL-6 for their shared receptor subunit gp130. In RA synovium, IL-27 can inhibit FLS production of IL-6 under TNF-α or IL-17A stimulation. IL-27 can inhibit the differentiation of naive CD4+ T cells into Th17 cells and suppress Th17 cell development through STAT1-dependent pathways, thereby reducing IL-17 production. IL-27 can also inhibit TNF-α-induced CCL20 production, indirectly impeding the recruitment of CCR6+ cell populations including Th17 cells, thereby reducing IL-17 secretion.

In terms of pathogenic effects, IL-27 can aggravate RA by inducing FLS expression of adhesion molecules and releasing inflammatory chemokines. IL-27 can activate the mTOR signaling pathway, leading to dysregulation and functional abnormalities of B cells in peripheral blood. Notably, gut-resident Treg cells also produce IL-27 during intestinal inflammation to limit potential Th17 differentiation, thereby suppressing pro-inflammatory effects against gut bacteria and alleviating intestinal damage under autoimmune and autoinflammatory conditions. IL-27 and IL-10 are produced by different Treg cell groups. The specific mechanism by which IL-27 acts as a Treg cell-derived inhibitor of intestinal Th17 responses remains unclear, and may involve signaling through STAT1 and STAT3 receptors.

V. Role of IL-27 in Antiviral Immunity.

IL-27 can impede HIV replication in various immune cells including PBMCs, CD4+ T cells, MDMs, and DCs. Its mechanisms of action may include: activating antiviral protein genes in CD4+ T cells; regulating the Th1/Th2 ratio; inducing IFI6 expression in MDMs; upregulating the immune restriction factors APOBEC3G and BST-2 in macrophages; and downregulating the host factor SPTBN1 and inhibiting YB-1 acetylation to exert its inhibitory effects. These diverse antiviral mechanisms indicate that IL-27 plays multi-layered regulatory roles in host immune responses defending against viral infections.

VI. Conclusion.

In IL-27-related basic research and drug development, high-quality recombinant IL-27 protein is a core tool for dissecting its signal transduction mechanisms and evaluating its immune regulatory functions. To address the needs of IL-27 functional research and cross-species comparison, UniBio provides IL-27 His Tag Protein, Cynomolgus. This product is suitable for application scenarios including binding activity analysis of IL-27 with IL-27Rα/gp130 receptors, JAK/STAT signaling pathway mechanism research, and functional studies of IL-27 in tumor immunity, autoimmune diseases, and metabolic regulation.

As an important member of the IL-6 family, IL-27, by virtue of its broad regulatory capacity over multiple cell types including T cells, B cells, NK cells, macrophages, and adipocytes through the IL-27R/JAK-STAT signaling pathway, exhibits complex pleiotropic functions in tumor immunity, obesity-related inflammation, autoimmune diseases, and antiviral immunity. Its bidirectional regulatory characteristics—between anti-tumor and pro-tumor, inhibiting obesity and promoting obesity, and anti-inflammatory and pro-inflammatory—suggest that IL-27 functions are highly context-dependent. IL-27 His Tag Protein, Cynomolgus provides reliable tool support for in-depth analysis of the IL-27 signaling network and cross-species functional comparison studies, and will continue to drive in-depth exploration in the field of immune regulation.

This article is reviewed and published by the technical expert team of UA

Disclaimer: This article partially utilizes artificial intelligence assistance in its creation. If any content involves copyright or intellectual property issues, please let us know and we promise to verify and remove it as soon as possible.

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