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E3 Ligases in T Helper 2-mediated Pathogenesis

Anupama Sahoo, Beatrisa Lerman, Andrei Alekseev and Roza Nurieva

Development of immunological tolerance has emerged as a critical mechanism for prevention of inflammatory and autoimmune diseases. Of the T helper (Th) subsets, the Th2 cells are the major players in allergic airway inflammation. Work in the past decade has been focused on active regulators of the Th2 differentiation program; however, the mechanisms that control Th2-mediated inflammation are poorly understood. E3 ubiquitin ligases (Cbl-b, Itch and GRAIL) which are implicated in T cell tolerance induction have been acknowledged as crucial factors in controlling the development and function of pro-allergic Th2 cells. Understanding of the molecular mechanisms underlying the function of these ligases in Th2 cells will lead to development of pharmacological approaches to promote the tolerance state in Th2 cells in order to treat allergic inflammation.