Project A08
The role of non-canonical NF-κB signaling in Treg cells in tissue homeostasis and disease
Background
Members of the canonical NF-κB signaling pathway are crucial regulators of Treg cell development, activation, and function, yet, the involvement of non-canonical NF-κB members is less well understood. Two core components of the non-canonical NF-κB signaling constitute the NF-κB-inducing kinase (NIK) and p52. Interstingly, IκBζ, a known transcriptional co-factor of canonical NF-κB signaling, is induced by NIK overexpression. Moreover, it is known that IκBζ can interact with p52.
We hypothesize that NIK, p52, and IκBζ play important roles in regulating the development, activation, and function of Treg cells in homeostasis and inflammation.
Strategy
By using T cell- and Treg cell-specific knockout mouse lines for NIK, p52, and IκBζ we aim to dissect the functional consequences of these molecules for Treg cell development, maintenance, suppressive function, cytokine response, and Treg cell-mediated tissue repair in homeostasis and during colitis. We further focus on the interconnection of the pathways in Treg cells by identifying common and unique target genes and interaction partners.