Upon activation, CD4+ T cells differentiate in different subsets of effector T helper (Th) cells which produce selective cytokines (IFN-g, IL-17, GM-CSF) and have specialized effector functions. Each subset of Th cells orchestrates a specific immune response dedicated to clear pathogens, but when dysregulated, can also lead to the development of autoimmune and allergic reactions.
CD4+ Th cell differentiation is driven by local cytokine environment. T cells producing IL-17 have been implicated in several autoimmune diseases including rheumatoid arthritis (RA), multiple sclerosis (MS), and psoriasis. Few years ago, Dr. Bettelli identified the cytokines IL-6, TGF-b and IL-23, which drive the differentiation and pathogenicity of Th17 cells. Recent studies have demonstrated that pathogenic Th cells also secrete GM-CSF. The Bettelli Lab is currently determining whether and how GM-CSF+ Th cells differ from IFN-g+ and IL-17+ Th cells and how they mediate their pathogenic functions in autoimmune diseases.
Additional Research Projects
Control of the Immune Response by DOCK8
The lab has been studying the mechanisms by which DOCK8 modulates the function of adaptive and innate cells and contributes to the progression of autoimmunity.
Mechanisms of T Cell Regulation
The Bettelli Lab has discovered that Th cells producing IFN-g, IL-17 and GM-CSF are differentially regulated by Tregs during the course of central nervous system (CNS) autoimmunity.
Modulation of the Immune Response by STAT1
Using loss and gain of function models, the Bettelli Lab is currently investigating how STAT1-mediated signaling modulates the function of different immune cells and participates in the pathogenesis of different autoimmune diseases.
