Interleukin-10 (IL-10) is a cytokine in the mouse immune system with potent anti-inflammatory and immunosuppressive functions. Its primary role is to control immune responses, preventing them from becoming overactive and damaging tissues. This regulation is important for maintaining immune homeostasis, a balanced state that protects the body. The discovery of IL-10 revealed a mechanism the immune system uses to police itself, ensuring responses are powerful but controlled.
Cellular Sources and Receptors of IL-10
A diverse array of immune cells in mice produces IL-10. Key producers include subsets of T cells, particularly regulatory T cells (Tregs), as well as monocytes, macrophages, B cells, and dendritic cells. This broad range of sources means IL-10 can be deployed in many immune scenarios. The context of the immune challenge dictates which cell type becomes the dominant producer.
The effects of IL-10 are mediated through its specific receptor, the IL-10 receptor (IL-10R). This receptor is a tetrameric complex composed of two IL-10R1 subunits and two IL-10R2 subunits. The IL-10R1 subunit binds directly to IL-10, while the IL-10R2 subunit is an accessory protein required for signaling to begin.
The widespread expression of the IL-10R on cells like macrophages and dendritic cells is fundamental to IL-10’s broad immunomodulatory capacity. Monocytes and macrophages show high levels of IL-10R expression, making them primary targets for its suppressive signals. The presence of this receptor determines whether a cell can respond to IL-10.
Mechanism of Immunosuppression
When IL-10 binds to its receptor, it initiates an intracellular cascade driven by the Janus kinase/signal transducer and activator of transcription (JAK-STAT) pathway. This binding activates two enzymes, JAK1 and Tyk2, which are associated with the receptor’s intracellular domains.
These activated enzymes phosphorylate a protein called STAT3. This phosphorylation causes STAT3 proteins to pair into dimers and move from the cytoplasm into the cell’s nucleus. Inside the nucleus, the activated STAT3 dimers act as transcription factors, binding to specific DNA sequences to regulate gene expression.
The primary outcome of this signaling is suppressing pro-inflammatory gene expression. Activated STAT3 inhibits the production of several inflammatory cytokines, including:
- Tumor necrosis factor-alpha (TNF-α)
- IL-1β
- IL-6
- IL-12
IL-10 signaling also downregulates major histocompatibility complex (MHC) class II molecules on antigen-presenting cells. Reducing MHC class II levels impairs their ability to present antigens to T cells, which dampens the adaptive immune response.
Role in Murine Disease Models
The function of IL-10 is demonstrated in mouse models of human diseases, where its absence or presence alters outcomes. For instance, in studies of inflammatory bowel disease (IBD), mice engineered to lack the IL-10 gene (Il10-/-) spontaneously develop severe colitis. Without IL-10’s suppressive signals, the immune response to gut microbes becomes uncontrolled, leading to chronic inflammation that mirrors the human condition.
In autoimmune disorders, IL-10 also plays a regulatory role. Experimental autoimmune encephalomyelitis (EAE), a mouse model for multiple sclerosis, shows this effect. In EAE models, administering IL-10 or enhancing its production can limit inflammation in the central nervous system, reducing paralysis and pathology by suppressing the self-reactive T cells that drive the attack.
The role of IL-10 in infectious disease models is more complex, showcasing its dual nature. During certain infections, IL-10 is beneficial because it prevents immunopathology—tissue damage caused by an overly aggressive immune response to a pathogen. However, this same immunosuppressive function can be detrimental by hindering pathogen clearance, potentially leading to a chronic infection.
Experimental Tools and Applications
The study of mouse IL-10 has been advanced by specific laboratory tools. The most foundational is the IL-10 knockout (IL-10-/-) mouse. By creating a mouse that cannot produce IL-10, scientists observed the direct consequences of its absence, which established its role in preventing spontaneous colitis and controlling inflammation.
Another widely used tool is recombinant mouse IL-10 (rIL-10). This laboratory-produced protein can be added to cells in culture (in vitro) to study its direct effects on cellular signaling and gene expression. It can also be administered to mice (in vivo) to assess its potential as a therapeutic agent for inflammatory or autoimmune conditions.
Measuring IL-10 levels and identifying the cells that produce it are also routine applications. An enzyme-linked immunosorbent assay (ELISA) is a common method used to quantify the concentration of IL-10 protein in samples like blood serum. To pinpoint which cells are making IL-10, researchers use intracellular cytokine staining followed by flow cytometry, which identifies cell markers and the presence of IL-10 inside the cell.