IL-25 joins T_H2 team

T-helper type 2 (T_H2) cell responses have a new star player. In the January issue of Immunity, Madeline Fort and co-workers report the discovery of a new cytokine — IL-25 — and show that it promotes T_H2-associated pathology.

IL-25 was identified in database searches for new molecules with homology to the proinflammatory cytokine IL-17. Il25 mRNA is produced by polarized T_H2 cells but not by naive T cells, T_H1 cells or other cell types. To test the biological functions of IL-25, mice were treated with the purified protein. Unlike IL-17, IL-25 treatment leads to characteristic T_H2 effects — increased serum IgG1 and IgE concentrations, increased eosinophil production, and inflammation of the lungs and gut.

So, does IL-25 mediate these effects by inducing the production of T_H2-type cytokines (IL-4, IL-5 and IL-13)? Quantitative PCR analysis of whole tissues confirmed that IL-25 treatment induces T_H2-type, but not T_H1-type, cytokine production. The roles of IL-4, IL-5 and IL-13 in mediating the effects of IL-25 were verified in vivo. However, identifying the responder cells was more difficult. In vitro assays of fractionated cell populations ruled out CD4⁺ T cells, B cells, monocytes, macrophages, eosinophils and NK cells. Instead, IL-5 and IL-13 production in response to IL-25 was attributed to a rare, lineage-negative cell that expresses high levels of MHC-class-II molecules. However, the source of IL-25-induced IL-4 was not identified.

This study indicates that IL-25 might be involved in promoting T_H2 responses and could be a target for the treatment of allergy and asthma.