Zeb2, also known as Sip1 and Zfhx1b, is a zinc finger E-box binding homeobox transcription factor. It is a master regulator of cellular plasticity involved in multiple biological processes, such as neuronal development, hematopoiesis, and the immune response [4,5,7]. In the context of the immune system, it has been associated with pathways related to B-cell and T-cell development and function, as well as autoimmune disease pathogenesis [1,2,3]. Mouse models, including gene knockout (KO) and conditional knockout (CKO) models, have been crucial in understanding Zeb2's functions in vivo.

In B-cell research, Zeb2 has been shown to be essential for the differentiation of age-associated B cells (ABCs) in both humans and mice. Zeb2 haploinsufficient individuals and mice lacking Zeb2 in B cells have reduced ABCs. In TLR7-driven lupus mouse models, Zeb2 is necessary for ABC formation and autoimmune pathology. Zeb2 binds to the +20-kb myocyte enhancer factor 2b (Mef2b)'s intronic enhancer, repressing MEF2B-mediated germinal center B cell differentiation and promoting ABC formation. It also targets genes important for ABC specification and function, like Itgax [1]. Similarly, in another study, Zeb2 was found to be required for the formation of CD11c+ atypical B cells in mice, which are important for controlling persistent infection by sustaining germinal center responses. Zeb2 haplo-insufficient Mowat-Wilson syndrome (MWS) patients have decreased circulating ABCs [6]. In CD4+ T cells, an age-associated T helper (THA) cell subset's B-cell-promoting functions are regulated by Zeb2 in autoimmunity [3].

In conclusion, Zeb2 is a multifunctional transcription factor with key roles in neuronal development, hematopoiesis, and immune-related processes. KO and CKO mouse models have been instrumental in revealing its function in autoimmune diseases, specifically in relation to the development and function of B cells and certain T-cell subsets, highlighting its potential as a therapeutic target in these disease areas [1,3,6].