The Hippo signaling pathway, originally discovered in Drosophila, is an evolutionarily conserved signaling pathway that controls cell proliferation, differentiation, and apoptosis during development. Recently, numerous studies have shown that Hippo signaling plays an important role in regulating both innate and adaptive immune response. For example, Hippo signaling (i) modulates bactericidal activity and anti-viral responses in innate immune cells; (ii) regulates lymphocyte migration, homing, and differentiation, and (iii) enhances antigen presenting activity by integrating metabolic activity and cytokine signaling in dendritic cell subsets.

Unlike the canonical Mst-Lats-Yap Hippo signaling cassette, which controls tissue growth during development and regeneration, most studies related to Hippo signaling in immune regulation, such as those on lymphocyte migration, T cell activation and differentiation, B cell maturation and phagocyte bactericidal activity, have focused on its core kinases, Mst1/2. Indeed, patients bearing a loss-of-function mutation of Mst1, the core kinase of the Hippo pathway, are reported to have an autosomal recessive primary immunodeficiency syndrome. Mst1/2 are known to cross-talk with other essential pathways in different immune cell types, such as integrin signaling, TLR signaling, IL-2R signaling and MAPK signaling.

The alternate upstream regulators or downstream effectors of Mst1/2 kinase in immune cells, such as the upstream Rap1-RAPL signals and the downstream PKC, DOCK8, or FOXO, have revealed the complex regulation of non-canonical Hippo signaling pathways. Progress in this field will be beneficial for the design and development of potential therapeutic agents for infections and autoimmune diseases, as well as tumor immunotherapy, by manipulating the Hippo pathway.

This Research Topic will provide a comprehensive overview of the functions of Hippo signaling in innate and adaptive immunity during homeostasis and in the presence of infection and/or disease. We welcome the submission of Reviews, Mini-Review, Original Research, Perspective and Commentary articles covering animal and human-based studies that address the following areas:

1. Role of Hippo signaling in innate immune cells.
2. Interplay between Hippo signaling and innate receptor signaling.
3. Role of Hippo signaling in T lymphocytes.
4. Role of Hippo signaling in B lymphocytes.
5. Hippo signaling in immune responses to bacterial infection.
6. Hippo signaling in immune responses to viral infection.
7. Interplay between Hippo signaling and cytokine receptor signaling.
8. Role of Hippo signaling in the metabolic regulation of innate and adaptive immune cells.
9. Hippo signaling and stress responses in immune cells, with a particular focus on oxidative stress and hypoxic stress.
10. Hippo signaling in the regulation of cell death in innate and adaptive immune cells.

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Frontiers in Immunology

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