Veterinary and Biomedical Sciences, Department of


Date of this Version



Published in final edited form as: J Immunol. 2021 November 01; 207(9): 2205–2215. doi:10.4049/jimmunol.2100565.

HHS Public Access Author manuscript J Immunol. Author manuscript; available in PMC 2022 November 01.


The Journal of Immunology is Copyright © 2018 by The American Association of Immunologists, Inc.


The discovery of interleukin (IL)-10 more than 30 years ago marked the beginning of our understanding of how cytokines regulate immune responses, based on cross-regulation between T helper (Th)1 and Th2 cytokines. Although multiple cell types were shown to produce IL-10, its identity as a Th2 cytokine remained strong since it was rigidly associated with Th2 clones in mice, whereas both Th1 and Th2 clones could secrete IL-10 in humans. However, as new Th1/Th2 cell functionalities emerged, anti-inflammatory action of IL-10 gained more attention than its inhibitory effect on Th1 cells, which may occur as an indirect consequence of suppression of antigen-presenting cells. This notion is also supported by the discovery of Treg cells whose suppressor functions involve the mediation of IL-10, among other molecules. From this perspective, we discuss the functionalities of IL-10 by highlighting important differences between mice and humans with an emphasis on Th1 and Th2 paradigm.