WDFY4, also known as WD repeat- and FYVE domain-containing protein 4, is a member of the BEACH (Beige and Chediak-Higashi) domain-containing family. It plays essential roles in the immune system, especially in the cross-presentation of classic dendritic cells, reactive oxygen species-induced apoptosis of CD8+ T cells, and non-canonical autophagic activity in B cells [3].

In gene knockout (KO) mouse models, Wdfy4 -/- mice fail to prime virus-specific CD8+ T cells in vivo or induce tumor rejection, indicating its crucial role in cross-presentation for antiviral and antitumor immunity [1]. In NOD mice, inactivation of Wdfy4 using Nuclease technology (NOD.Wdfy4 -/-) ameliorates autoimmune diabetes and insulitis, suggesting that priming of autoreactive CD8+ T cells in NOD mice requires cross-presentation by cDC1, which depends on Wdfy4 [2]. Lack of Wdfy4 in mice promotes Th2 cell differentiation, aggravating ovalbumin-induced asthma [4]. Also, selective deficiency of Wdfy4 in T cells leads to a reduction in the number of CD8+ T cells via reactive oxygen species-induced apoptosis, promoting tumor growth [5]. In B cells, loss of Wdfy4 in Wdfy4 conditional knockout (CKO) mice decreases the number of total B cells and some B cell subpopulations, alleviating SLE phenotypes [6].

In conclusion, WDFY4 is vital for multiple immune-related functions, including cross-presentation, T-cell and B-cell regulation. The use of Wdfy4 KO and CKO mouse models has significantly advanced our understanding of its roles in antiviral, antitumor immunity, and autoimmune diseases such as diabetes, asthma, and SLE.