| First Author | Ferreira ACF | Year | 2023 |
| Journal | Immunity | Volume | 56 |
| Issue | 7 | Pages | 1468-1484.e7 |
| PubMed ID | 37285842 | Mgi Jnum | J:337870 |
| Mgi Id | MGI:7508976 | Doi | 10.1016/j.immuni.2023.05.010 |
| Citation | Ferreira ACF, et al. (2023) Neuroprotective protein ADNP-dependent histone remodeling complex promotes T helper 2 immune cell differentiation. Immunity 56(7):1468-1484.e7 |
| abstractText | Type 2 immune responses are critical in tissue homeostasis, anti-helminth immunity, and allergy. T helper 2 (Th2) cells produce interleukin-4 (IL-4), IL-5, and IL-13 from the type 2 gene cluster under regulation by transcription factors (TFs) including GATA3. To better understand transcriptional regulation of Th2 cell differentiation, we performed CRISPR-Cas9 screens targeting 1,131 TFs. We discovered that activity-dependent neuroprotector homeobox protein (ADNP) was indispensable for immune reactions to allergen. Mechanistically, ADNP performed a previously unappreciated role in gene activation, forming a critical bridge in the transition from pioneer TFs to chromatin remodeling by recruiting the helicase CHD4 and ATPase BRG1. Although GATA3 and AP-1 bound the type 2 cytokine locus in the absence of ADNP, they were unable to initiate histone acetylation or DNA accessibility, resulting in highly impaired type 2 cytokine expression. Our results demonstrate an important role for ADNP in promoting immune cell specialization. |
