Hippo Pathway in Mammalian Adaptive Immune System

The Hippo pathway was originally identified as an evolutionarily-conserved signaling mechanism that contributes to the control of organ size. It was then rapidly expanded as a key pathway in the regulation of tissue development, regeneration, and cancer pathogenesis. The increasing amount of evidence in recent years has also connected this pathway to the regulation of innate and adaptive immune responses. Notably, the Hippo pathway has been revealed to play a pivotal role in adaptive immune cell lineages, as represented by the patients with T- and B-cell lymphopenia exhibiting defective expressions of the pathway component. The complex regulatory mechanisms of and by the Hippo pathway have also been evident as alternative signal transductions are employed in some immune cell types. In this review article, we summarize the current understanding of the emerging roles of the Hippo pathway in adaptive immune cell development and differentiation. We also highlight the recent findings concerning the dual functions of the Hippo pathway in autoimmunity and anti-cancer immune responses and discuss the key open questions in the interplay between the Hippo pathway and the mammalian immune system.