Foxe1, also known as TTF-2, is a thyroid-specific transcription factor essential for thyroid gland development and maintenance of the differentiated state. It is involved in regulating multiple biological processes and is associated with pathways related to cell proliferation, differentiation, and immune cell recruitment [2,3]. Genetic models, such as gene knockout (KO) mouse models, have been crucial in studying its functions.

In psoriasis, FOXE1 expression is increased in lesional skin. Knockdown of FOXE1 in keratinocytes (KCs) reduces their proliferation, cytokine production (IL-1β, IL-6, and TNF-α), and ameliorates dermatitis symptoms in imiquimod-induced psoriasis-like mouse models, indicating its role in psoriasis pathogenesis [1].

In thyroid-related studies, FOXE1 gene dosage reduction in mice affects thyroid cancer histology, differentiation, and macrophage infiltration. Heterozygous FOXE1 null allele (FOXE1+/-) mice crossed with a BRAFV600E-inducible cancer model show that reduced FOXE1 leads to less malignant-like thyroid cancers with reduced proliferation and increased apoptosis but also severe undifferentiation. Additionally, FOXE1-expressing thyroid cells can regulate macrophage chemotaxis, and reduced FOXE1 dosage decreases pro-tumourogenic M2 macrophage infiltration in tumours [4,5]. In adult mice, Foxe1 deletion is associated with abnormal follicular architecture, hypothyroidism, and an increase in thyroidal mast cells [6].

In conclusion, Foxe1 is vital for thyroid gland development and function. Through model-based research, especially KO mouse models, it has been revealed to play significant roles in diseases like psoriasis and thyroid-related disorders, including cancer and hypothyroidism. Understanding Foxe1 functions provides insights into disease mechanisms and potential therapeutic targets.