# A Phylogenetic Perspective on the Evolutionary Patterns of the Animal Interleukin-10 Signaling System

## TL;DR

This paper traces the evolutionary history of the IL-10 signaling system in animals, revealing how it diversified and adapted across species.

## Contribution

The study provides a detailed phylogenetic analysis of IL-10 ligands and receptors across over 400 species, identifying evolutionary origins and functional subgroups.

## Key findings

- IL-10 receptors originated in cartilaginous fishes around 450 million years ago, while IL-10 ligands diversified in bony fishes around 400 million years ago.
- Functional divergence led to immunosuppressive, barrier-protective, and antiviral subgroups within the IL-10 signaling system.
- Conserved structural motifs and evolutionarily invariant residues suggest potential therapeutic targets and epitopes.

## Abstract

Background: The interleukin-10 (IL-10) signaling system, comprising ligands (IL-10s) and receptors (IL-10Rs), plays critical roles in immune regulation, inflammation resolution, and disease pathogenesis. “IL-10 signaling system” here refers to the immunomodulatory signaling system composed of ligands (IL-10s) and receptors (IL-10Rs), which belong to different Protein families in evolution, but achieve functional synergy through the conserved JAK-STAT pathway. Understanding their evolutionary and functional dynamics is essential for elucidating immune mechanisms and therapeutic targeting. Methods: Through phylogenetic reconstruction, homology analysis, and sequence alignment across >400 animal species, we traced the evolutionary trajectory and structural–functional diversification of IL-10s and IL-10Rs. Results and Conclusions: IL-10 signaling components emerged in early vertebrates, with IL-10Rs originating in cartilaginous fishes (~450 Mya) and IL-10s diversifying in bony fishes (~400 Mya). Functional divergence yielded immunosuppressive (IL-10), barrier-protective (IL-20 subfamily), and antiviral (type III IFN) subgroups. Structurally, conserved motifs (e.g., IL-10R1 GYXXQ, IL-22 N54-glycosylation) underpin receptor–ligand binding and JAK/STAT signaling. Evolutionarily invariant residues suggest candidate therapeutic epitopes. This study provides an evolutionary framework highlighting functional conservation and species-specific adaptation within IL-10 signaling, with implications for immunotherapy and animal breeding.