Cis-regulatory and epigenetic codes of innate immunity

Innate immune cells, including dendritic cells, macrophages (such as microglia), are essential for host defense and tissue homeostasis. Their identity and function depend not only on transcription factors but also on cis-regulatory elements and epigenetic mechanisms that control gene expression in the right cell types at the right developmental stages. Recent discoveries have highlighted enhancer modules as key drivers of cell fate, such as Irf8 enhancers for cDC1 specification and commitment, Zeb2 enhancers active in distinct myeloid and lymphoid lineages, and the Csf1r FIRE enhancer required for microglia survival and maintenance. Beyond enhancers, DNA methylation, histone modifications, and non-coding RNAs provide additional layers of regulation, enabling cells to adapt dynamically to developmental and environmental cues.This Research Topic aims to define the regulatory codes that shape innate immune diversity. While transcription factors like IRF8, ZEB2, and PU.1 are central to lineage specification, their activity is orchestrated by enhancer networks, promoter landscapes, and higher-order chromatin organization. In parallel, epigenetic modifications and non-coding RNAs stabilize or reprogram these identities during health and disease. We encourage submissions that illuminate how cis-regulatory and epigenetic mechanisms direct cell fate, memory, and functional plasticity across innate lineages. By integrating studies of dendritic cells, macrophages (including microglia), and related populations, this collection seeks to uncover common principles and context-specific regulation, advancing both fundamental immunology and translational opportunities.This Research Topic accepts Original Research, Systematic Review, Methods, Review and Mini-Review, Hypothesis & Theory, Clinical Trial, Classification, Technology and Code, Perspective, Case Report, Brief Research Report, General Commentary, Opinion. We welcome manuscripts focusing on, but not limited to, the following sub-topics:• Enhancer logic and transcription factor–cis-element interactions in innate immune cells• Chromatin modifications, DNA methylation, and non-coding RNA in lineage regulation• 3D genome organization and chromatin accessibility shaping immune fates• Regulatory mechanisms of innate immune cell identities and tissue adaptation Topic editors: Jang Hyun Park, Patrick Rodrigues, Sunkyung Kim, Feiya Ou Source: https://www.frontiersin.org/research-topics/74992/cis-regulatory-and-epigenetic-codes-of-innate-immunity