Zinc Finger Protein, Multitype 1, Suppresses Human Th2 Development via Downregulation of IL-4

Abstract

Background: Among several GATA family transcription factor-associating proteins, zinc finger protein, multitype 1 (ZFPM1), at least that of murine origin, has been shown to modulate the activity of GATA-3. However, the functional role of human ZFPM1 in the immune system has not been elucidated. Therefore, we here investigated the contribution of ZFPM1 to human Th1/Th2 differentiation. Methods: The cDNA of ZFPM1 was cloned and introduced into human cord blood CD4+ T cells by a lentiviral transduction system. Then, the expression of IL-4 and IFN-γ mRNA was determined by quantitative real-time RT-PCR. The effect of ZFPM1 on the promoter activity of IL-4 and IFN-γ in Jurkat cells was also investigated. Results: Stimulation-induced expression of IL-4 and IFN-γ in human CD4+ T cells was suppressed and enhanced, respectively, by the introduction of ZFPM1. The transcriptional activity of IL-4 was also diminished by ZFPM1, whereas that of IFN-γ was not affected. Conclusion: ZFPM1 that facilitates human Th1 differentiation via the downregulation of IL-4 is a potential target for the treatment of allergic diseases.

The nasal methylome as a biomarker of asthma and airway inflammation in children

“…Lower DNAm of CLC , a gene for lysophospholipase expressed in eosinophils, was associated with current asthma, allergic asthma, and FeNO. The ZFPM1 gene known to facilitate Th1 differentiation through the downregulation of the Th2 cytokine IL-4 20 had lower DNAm levels for participants with higher levels of FeNO (DMR), total IgE, environment IgE sensitization, asthma, and allergic asthma.…”

Maternal phthalate exposure promotes allergic airway inflammation over 2 generations through epigenetic modifications

“…In the offspring of BBP-exposed dams, we identified 13 genes fulfilling these criteria, including 3 interesting candidates involved in immune processes contributing to T H 2 differentiation and therefore resulting in a higher susceptibility to experience allergic diseases. 35,36,38 Considering the longitudinal stability of differential RNA expression induced by maternal BBP exposure from 3-week-old pups to the adult offspring, Fanca and Zfpm1 appeared to be the most promising genes. Characterizing the CD4 1 T-cell function from offspring of BBP-exposed dams primarily revealed an increased susceptibility for a T H 2-driven immune response, as expected from downregulation of the GATA-3 repressor Zfpm1.…”

“…36 Third, we focused on Zfpm1, also known as friend of GATA protein 1 (Fog1), a gene that acts as a repressor of GATA-3-mediated T H 2 cell development. [37][38][39] Therefore downregulation of Zfpm1 could promote a T H 2-driven immune response. Validation of our RNA-sequencing results by using real-time PCR confirmed a reduced expression of all 3 genes in CD4 1 T cells from 3-week-old offspring of BBP-exposed dams compared with control animals (Fig 6, C).…”

An epigenome-wide association study of total serum IgE in Hispanic children

“…These four CpG sites were located in the genes for zinc-finger protein multi-type 1 ( ZFPM1 ), acyl-CoA thioesterase 7 ( ACOT7 ), and meiotic nuclear division 1 ( MND1 ). ZFPM1 suppresses expression of interleukin 4 (IL-4) and induces expression of IFN-γ in CD4+ T cells, thus reducing Th2 cell differentiation 29 . Moreover, WBC DNA methylation in both ZFPM1 and ACOT7 has been associated with asthma 30 , and WBC DNA methylation of ZFPM1 was consistently associated with atopy (defined as at least one positive IgE to allergens) or high total IgE (≥200 kU/L) across two Caucasian cohorts included in a prior study 31 .…”