Project description:Epidermal keratinoyctes consitute the primary physical and biological barrier of the skin. The goal of this study is to determine the functions of keratinocyte UBE2N in regulation of skin homeostasis and immunity.
Project description:The existence of immunoregulatory mechanisms that control autoimmunity in non-lymphoid tissues remains unclear. Through transcriptomic and lipidomic analyses, we found that psoriasis is tightly associated with a significant downregulation of fatty acid metabolism and biosynthesis pathways as well as Th2 signature genes. Among lipids-activated transcription factors, LXR and PPAR were required for fatty acid homeostasis and resistance to psoriasis in mice. STAT6 played a role in the homeostatic expression of LXR and PPARγ in the skin. Additionally, innate lymphoid cells established tonic type 2 immunity in normal skin by producing IL-13 continually. Mice lacking tonic type 2 immunity were more susceptible to psoriatic inflammation in vivo. In human skin, inhibiting tonic type 2 immunity worsened psoriasis-like inflammation and IL-17 production, while activating LXR or PPAR inhibited them. Therefore, tonic type 2 immunity is an essential tissue checkpoint that represses autoimmunity and maintains lipid homeostasis in the skin.
Project description:Skin homeostasis is guided by spatiotemporal regulation of gene expression, establishing each stage of keratinocyte differentiation. The current study presents transcriptomic and chromatin profiling for the proliferating (basal) and differentiated (suprabasal) cell populations derived from neonate mice (p0-p2) skin epidermis. This multi-omic approach will enable idenitification of cell specific epidermal cross-talk central to the equlibirum.
Project description:Foxp3+ T-regulatory (Treg) cells maintain immune homeostasis and limit autoimmunity, but can also curtail host responses to cancers. Tregs are therefore promising targets to enhance anti-tumor immunity. Histone/protein acetyltransferases (HATs) promote chromatin accessibility, gene transcription and the function of multiple transcription factors and non-histone proteins. We found that conditional deletion or pharmacologic inhibition of one specific HAT, p300, in Foxp3+ Tregs, increased TCR-induced apoptosis in Tregs, impaired Treg suppressive function and iTreg peripheral conversion, and limited tumor growth in immunocompetent, but not in immunodeficient, hosts. Our data demonstrate that p300 is important for Foxp3+ Treg function and homeostasis in vivo and in vitro, and identify a novel mechanism to diminish Treg function without overtly impairing effector Tcell responses or inducing autoimmunity. Collectively, these data suggest a new approach for cancer immunotherapy. RNA from three independent samples from magnetically separated CD4+CD25+ Treg of fl-p300/Foxp3cre mice, compared to wild type (Foxp3cre) control (all C57Bl/6 background).
Project description:Skin homeostasis is guided by spatiotemporal regulation of gene expression, establishing each stage of keratinocyte differentiation. The current study presents transcriptomic and chromatin profiling for the proliferating (basal) and differentiated (suprabasal) cell populations derived from neonate mice (p0-p2) skin epidermis. This multi-omic approach will enable idenitification of cell specific epidermal cross-talk central to the equlibirum.