IL10: A key anti-inflammatory cytokines in the immune system

• Gene Information: Interleukin 10 (IL10) is a protein-coding gene located on chromosome 1q32.1. It encodes anti-inflammatory cytokine that restrains immune activation and shapes inflammatory responses.
• Protein Expression: The expression level of IL-10 is relatively high in lymphoid tissues as well as in barrier organs such as the intestine and skin. The main cell sources of IL-10 are monocytes/macrophages and regulatory T cells.
• Signaling Pathway:  IL-10 signals through a heterotetramer comprising IL-10RA and IL-10RB, leading to JAK1/STAT3-dependent transcriptional upregulation of anti-inflammatory factors. This in turn inhibits both the production of pro-inflammatory cytokines (e.g., TNF-α, IL-6) and the antigen-presenting activity of macrophages and monocytes.
• Therapeutic Inhibition: Blocking the binding of IL10 to its receptor will lead to an increase in pro-inflammatory cytokines, thereby increasing the risk of autoimmune immunity. The most representative consequence occurs in the intestine, resulting in spontaneous colitis.

IL10

• The exons 1-5 of mouse Il10 gene that encode the full-length protein were replaced by human IL10 exons 1-5 in B-hIL10 mice(C).
• The promoter, 5’UTR and 3’UTR region of the mouse gene were retained. The human IL10 expression was driven by endogenous mouse Il10 promoter, while mouse Il10 gene transcription and translation will be disrupted.

• Human IL10 mRNA was exclusively detectable in homozygous B-hIL10 mice(C) but not in wild-type mice.

Strain specific analysis of IL10 mRNA expression in wild-type BALB/cCrSlcNifdc mice and homozygous B-hIL10 mice(C) by RT-PCR. Spleen RNA were isolated from wild-type BALB/cCrSlcNifdc mice (+/+) and homozygous B-hIL10 mice(C) (H/H), then cDNA libraries were synthesized by reverse transcription, followed by PCR with mouse or human IL10 primers. Mouse Il10 mRNA was only detectable in wild-type BALB/cCrSlcNifdc mice. Human IL10 mRNA was exclusively detectable in homozygous B-hIL10 mice(C) but not in wild-type mice.

• Human IL10 was only detectable in homozygous B-hIL10 mice(C) but not in wild-type BALB/cCrSlcNifdc mice.

Strain specific IL10 expression analysis in homozygous B-hIL10 mice(C) by ELISA. Serum were collected from wild-type BALB/cCrSlcNifdc mice (+/+) and homozygous B-hIL10 mice(C) (H/H) stimulated with LPS in vivo for 2 hrs, and analyzed by ELISA with species-specific mouse IL10 ELISA kit (Biolegend, 431414) and human IL10 ELISA kit (Biolegend, 430604). Mouse IL10 was only detectable in wild-type BALB/cCrSlcNifdc mice. Human IL10 was only detectable in homozygous B-hIL10 mice(C) but not in wild-type mice. Values are expressed as mean ± SEM. ND: not detectable.