Irf4, a transcription factor in the interferon regulatory factor (IRF) family, is crucial for immune cell development and function [2][3][4]. It mediates critical immune responses via interactions with upstream signaling pathways like the T-cell receptor and B-cell receptor pathways, and their binding partners in normal lymphocyte development and immunity [2]. It also plays key roles in controlling B cell to plasma cell differentiation and immunoglobulin class-switching [6].

Deleting Arid1a in activated murine B cells, which is required for Irf4 expression, disrupts Irf4-dependent transcriptional networks and blocks plasma cell differentiation [1]. A knock-in mouse model of heterozygous T95R mutation in Irf4 showed a severe defect in antibody production, consistent with the autosomal dominant combined immunodeficiency observed in patients with this mutation [3]. Reducing Irf4 expression in antigen-specific T cells from mice infected with lymphocytic choriomeningitis virus restored their functional and metabolic properties and promoted memory-like T cell development, indicating Irf4 promotes T cell exhaustion during chronic infection [5].

In conclusion, Irf4 is essential for immune cell development, lymphocyte activation, and plasma cell differentiation. Mouse models, such as gene-knockout and knock-in models, have been instrumental in revealing its role in diseases like multiple myeloma, combined immunodeficiency, and during chronic infections, providing insights into its function and potential therapeutic targets.