Dissecting the role of TGF-b in the skin

Abstract

Abstract The skin is outermost barrier in the body. Its only breaches are represented by hair follicles, which represent the only point of entrance for all the skin-sitting pathogens and commensals. Therefore, they can be defined as the most immunologically active sites of the skin. As such, tight regulation is needed at these sites and it is achieved not only through immune cells, but also non-hematopoietic cells like keratinocytes and fibroblasts. Example of immune cells are regulatory T cells, which are not only activated by, but also produce large amounts of TGF-b, a multifunctional cytokine, present in the body in 3 isoforms (TGF-b1,2 and 3). These isoforms have been reported to be fundamental for skin development during organogenesis and additional findings report about their role in driving cell localization in the skin as well as involvement in tissue repair. Though, litte is known about their immunological role in the skin. Upon generating a working protocol to separate skin layers and isolate cells from them, we were able to start to define the cell composition of each layer both at steady state and during inflammation. Moreover, we could detect the three TGF-b isoforms in each layer at both gene and protein level further discriminating between hematopoietic and non-hematopoietic sources. Finally, the importance of TGF-b in the skin was confirmed by experiments on TGF-b receptor I depleted mice. For the future, we are planning on defining exactly which cells secrete and respond to TGF-band confirm these findings by generating conditional KO mice. Additionally, the role of TGF-b will be assessed in world-wide skin diseases. Intramural Research Program of NIDCR