Our main focus is to understand the mechanisms ensuring the tissue functionality in normal skin and characterize changes in terms of dynamics and functionality when skin homeostasis is jeopardized by deleterious signals in fragile skin, such as aged skin.
Project 1A. Role of the keratinocyte as sensor. Project leaders: B. Fromy & F. Chevalier
We have identified a key function of the thermoreceptor TRPV3, a heat-activated cation channel abundantly expressed in keratinocytes, in the vascular skin thermoregulation (Fromy et al. JID 2018). However, the question how TRPV3-expressing skin cells communicate with the vessels remains to be addressed. In addition, age-related alteration of this dialog and its relationship with skin function weakening is a major milestone in preventing heat-related health outcomes in the elderly.
This project aims 1) to decipher messenger signals involved in the communication between epidermal keratinocytes and dermal microvessels after TRPV3 activation and 2) to characterize how this communication is altered with aging. This innovative project, by focusing on keratinocyte as sensor or receptor of complex interactions with other skin cell types and skin structures, will shed light on the importance of intercellular communications in the skin and their perturbation in the aging tissue.
Reference:
Fromy B, Josset-Lamaugarny A, Aimond G, Pagnon-Minot A, Marics I, Tattersall GJ, Moqrich A*, Sigaudo-Roussel D*. Disruption of TRPV3 impairs heat-evoked vasodilation and thermoregulation: a critical role of CGRP. J Invest Dermatol. 2018; 138(3): 688-696.
Project 1B – Intercellular communication in the skin: dialog fibroblasts-kératinocytes using extracellular vesicles. Project leader: J. Lamartine
The behavior and survival of eucaryotic cells are mostly dependent to their ability to communicate with the surrounding cells. In the skin, a complex organ composed of multiple cellular populations, numerous cell-cell dialogs are established by various mechanisms of direct contact or distant interactions such as those involving extracellular vesicles (EVs) secreted by emitter cells and captured by recipient cells. These EVs carries a complex cargo of informative molecules. In this project, we want to study the dialog between epidermal keratinocytes themselves and between keratinocytes and dermal fibroblasts. We will explore the functional impact of this dialog and will identify the messengers transmitted by EVs. We are particularly interested by the effect of tissue aging on the cell-cell dialog and its impact of aged skin functionality. This work should allow to identify new mechanisms involved in the maintenance of the epidermal barrier function and the contribution of the dermis-epidermis dialog in this function.
Capture of extracellular vesicles (EVs labeled in red) by human epidermal keratinocytes
