We are now entering the third decade of the 21st Century, and, especially in the last years, the achievements made by scientists have been exceptional, leading to major advancements in the fast-growing field of Immunology. Frontiers has organized a series of Research Topics to highlight the latest advancements in research across the field of Immunology in 2022. This editorial initiative of particular relevance, led by Prof. Francesca Granucci Specialty Chief Editor of the Molecular Innate Immunity section, and Dr. Uday Kishore is focused on new insights, novel developments, current challenges, latest discoveries, recent advances, and future perspectives in the field of molecular innate immunity.

Innate immunity has a critical role in the early stage of the host defense response by the timely recognition of pathogenic or danger signals by various cell surface or cytoplasmic receptors. This is followed by signal transduction via various adaptor and effector molecules. The main functions of innate immunity are to identify and remove the invading pathogens, to recruit various immune cells to the site of infection, and to prepare the adaptive immune response. The Innate immune system has been intensively studied for several decades and now we can begin to understand this system on a molecular level.

As the outermost barrier of the body, the skin protects against bacterial, viral, and environmental assaults. To reach this end, epidermal and dermal resident cells have evolved intricate communication networks, involving innate and adaptive immune cells, epithelial cells, and neurons. In disease states, skin resident cells are aided by recruited immune cells, such as neutrophils, basophils, and eosinophils. Initially, these cell types were studied in isolation, but recent focus has shifted towards understanding how physical interactions between cells and communication initiated by soluble mediators facilitate coordinated immune responses in the cutaneous microenvironment to maintain homeostasis, preserve barrier function, and, effectively clear bacterial, viral or fungal assailants. In this Research Topic, the goal is to highlight recent advances in cutaneous biology and immunology to provide insight into the cellular networks underlying the generation and regulation of cutaneous immune responses. Recent advances in this area have described novel pathways regulating skin-resident memory T cells, keratinocytes-immune cell interactions, and the relationships between sensory neurons and immune cells in the skin. Cumulatively, these studies provide a framework for understanding the complex interactions that are necessary for maintaining host protection, and homeostasis and reveal novel targetable pathways for patients with skin disease.