Interleukin-10 (IL-10) is a crucial anti-inflammatory cytokine that plays a significant role in regulating immune responses. It is also known as human cytokine synthesis inhibitory factor (CSIF). In humans, IL-10 is encoded by the IL10 gene located on chromosome 1 . This cytokine is primarily produced by monocytes and, to a lesser extent, by lymphocytes, including type-II T helper cells (TH2), mast cells, CD4+ CD25+ Foxp3+ regulatory T cells, and certain subsets of activated T cells and B cells .
IL-10 is a homodimer, with each subunit consisting of 178 amino acids . It belongs to the class-2 cytokine family, which includes other cytokines such as IL-19, IL-20, IL-22, IL-24, and various interferons . The IL-10 protein signals through a receptor complex composed of two IL-10 receptor-1 and two IL-10 receptor-2 proteins . This receptor complex activates the STAT3 signaling pathway via the phosphorylation of the cytoplasmic tails of IL-10 receptor 1 and IL-10 receptor 2 by JAK1 and Tyk2, respectively .
The expression of IL-10 is tightly regulated at both the transcriptional and post-transcriptional levels. It is minimally expressed in unstimulated tissues and requires triggering by commensal or pathogenic flora . IL-10 expression involves extensive locus remodeling in monocytes upon stimulation of TLR or Fc receptor pathways . The induction of IL-10 involves ERK1/2, p38, and NF-κB signaling, with transcriptional activation via promoter binding of transcription factors NF-κB and AP-1 . Additionally, IL-10 expression is regulated at the post-transcriptional level, involving control of mRNA stability via AU-rich elements and microRNAs such as let-7 and miR-106 .
While IL-10 is a well-studied cytokine in both mice and humans, there are notable differences in its function and regulation between the two species. In mice, IL-10 is rigidly associated with TH2 clones, whereas in humans, both TH1 and TH2 clones can secrete IL-10 . This difference highlights the complexity of IL-10’s role in immune regulation and its varying effects across species.
IL-10 has significant therapeutic potential due to its anti-inflammatory properties. It has been explored in various clinical settings to modulate immune responses and treat inflammatory diseases . For instance, IL-10 has been shown to inhibit the activation of human myeloid cells in response to TLR activation . Additionally, IL-10 suppression has been found to enhance T-cell antitumor immunity, making it a potential target for cancer immunotherapy .