Work

IL-33 expands plasma cells, disrupts germinal centers, and increases autoantibody production in mice

Year: 2025

Type: article

Abstract: IL-33 is an inflammatory cytokine contributing to asthma, Chronic Obstructive Pulmonary Disease (COPD), and autoimmune diseases. Although recent studies suggest that IL-33 can induce the generation of autoantibodies, the role of IL-33 on B cell maturation and tolerance is poorly understood. Here, by inducing systemic overexpression of IL-33 in mice, we show that this cytokine induces the IL-5 and CD4 T cell-dependent accumulation of plasmablasts and plasma cells of all isotypes in the spleen, and leads to an increased antibody production. IL-33 also disrupts splenic architecture and elevates autoantibody production, indicating a break in peripheral tolerance. Consistently, elevated levels of IL-33 exacerbate autoantibody production, kidney damage, and decrease survival in a mouse model of lupus. Additionally, intranasal delivery of IL-33 in mice exposed to house dust mite extract (HDM) increases autoantibodies in the lung. Notably, blocking IL-33 reduced the autoantibodies generated during HDM exposure, indicating that HDM-induced autoantibody production is IL-33 dependent. Thus, our findings implicate IL-33 in the break of peripheral B cell tolerance, opening new therapeutic avenues for the treatment of infection, COPD and autoimmune conditions. Elevated levels of IL-33 induce the production of autoantibodies through an unknown mechanism. Here, the authors show that IL-33 disrupts splenic architecture and germinal center organization, causing an expansion of antibody-secreting plasmablasts and plasma cells. In multiple mouse models of inflammation, administration of IL-33 exacerbates the pathology, increasing the production of autoantibodies, whereas IL-33 blockade reverses autoantibody production in a model of lung inflammation.

Source: Nature Communications

DOI: 10.1038/s41467-025-67867-2