Iden

Project summary

The skin acts as a dynamic interface between the organism and its environment and protects from uncontrolled water loss and external threats such as pathogens, toxins, mechanical damage and temperature variation. Its outermost stratified epidermis is continuous with epidermal appendages like hair follicles and sweat glands. Keratinocytes represent the most abundant cell type, but the epidermis also hosts other resident cell types with crucial functions for the organism: melanocytes mediate hair and skin pigmentation, protecting KCs from ultraviolet damage, whereas resident immune cell populations like Langerhans cells and dendritic epidermal T cells constitute a first line of defense against environmental pathogens and malignant transformation in murine skin. The epidermis is also innervated by sensory neurons via intra-epidermal free nerve endings that span all epidermal layers. How these epithelial, immune and neuronal cell types and networks are spatiotemporally coordinated within the densely packed epidermis to simultaneously ensure skin barrier, pigmentation, sensation and host defense is largely unresolved. Our recent work could delineate that epidermal polarity signaling and cell-cell adhesion modulate the fate and function of adjacent tissue-resident cell types (melanocytes, immune cells), and we obtained insights into signals that determine tissue-wide cell-type patterning. Moreover, we established improved coculture models for mechanistic studies of heterotypic crosstalk of epidermal cell-types.

In this project, we will employ interdisciplinary approaches at the molecular, cellular, and organ scales to gain a better molecular understanding of direct cell-cell communication between epithelial, immune and neuronal cell types in healthy and diseased skin. In vivo mouse models and advanced co-cultures of epidermis-resident cell types will be used to identify potential new molecular players at junctions between keratinocytes and their epidermis-resident neighbors. Moreover, we aim to reveal ultrastructural features of heterotypic junctions in wild-type and mutant epidermal tissues up to their tissue-level connectivity. Our goal within HetCCI is to reveal contact-dependent molecular and cellular mechanisms that underlie intercellular communication across the epithelial-immune-neuronal axis in skin. Embedded in the SPP 2493 consortium, we further expect to contribute to heterotypic cell-cell communication maps across epithelia of different organs and model organisms.