MST1 deficiency promotes B cell responses by CD4 + T cell-derived IL-4, resulting in hypergammaglobulinemia

Park, Eunchong; Kim, Myun Soo; Song, Jeong Hwa; Roh, Kyung Hye; Lee, Rana; Kim, Tae Sung

doi:10.1016/j.bbrc.2017.05.094

Cited by 14 publications

(12 citation statements)

References 16 publications

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“…Abnormalities in neutrophil viability have also been reported [ 69 ]. These pathologies are accurately recapitulated in Mst1/Stk4 -knockout mouse models [ 73 , 74 , 75 , 76 ]. Mst1/Stk4 -knockout mouse models have also been used to implicate MST1 in experimental autoimmune encephalomyelitis and collagen-induced arthritis [ 75 ].…”

Section: Immune Cell-intrinsic Hippo Signalingmentioning

confidence: 99%

“…Consistent with this, Salojin et al (2014) reported that MST1-deficient B lymphocytes were markedly unresponsive to mitogenic stimulation of the BCR in vitro and that MST1-deficient mice did not produce a significant humoral response to ovalbumin [ 75 ]. More recent evidence by Park et al suggests a more complex in vivo regulatory network, whereby MST1 mediates cross-talk between T regs , T h 2, and B lymphocytes [ 76 ]. In this model, MST1 deficient mice exhibited a hyperactivated B lymphocyte-mediated humoral response as a result of defective T reg immunomodulatory signaling, indicating multidirectional regulation between lymphocyte subtypes modulated by cell-intrinsic MST1 functions.…”

Section: Immune Cell-intrinsic Hippo Signalingmentioning

confidence: 99%

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The Hippo Pathway: Immunity and Cancer

Taha

Rensburg

Yang

2018

Cancers

131

101

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Since its discovery, the Hippo pathway has emerged as a central signaling network in mammalian cells. Canonical signaling through the Hippo pathway core components (MST1/2, LATS1/2, YAP and TAZ) is important for development and tissue homeostasis while aberrant signaling through the Hippo pathway has been implicated in multiple pathologies, including cancer. Recent studies have uncovered new roles for the Hippo pathway in immunology. In this review, we summarize the mechanisms by which Hippo signaling in pathogen-infected or neoplastic cells affects the activities of immune cells that respond to these threats. We further discuss how Hippo signaling functions as part of an immune response. Finally, we review how immune cell-intrinsic Hippo signaling modulates the development/function of leukocytes and propose directions for future work.

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Section: Immune Cell-intrinsic Hippo Signalingmentioning

confidence: 99%

Section: Immune Cell-intrinsic Hippo Signalingmentioning

confidence: 99%

The Hippo Pathway: Immunity and Cancer

Taha

Rensburg

Yang

2018

Cancers

131

101

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“…As MST1 is critical for the proper activities of FOXO, defective MST1–FOXO signaling impairs the differentiation and function of Treg cells, collapsing immune tolerance and thereby provoking autoimmunity [39,55]. Another study demonstrated that IL-4-rich environments created by MST1-deficient CD4 + T cells also contribute towards the uncontrolled B cell responses [67]. Together, these results not only highlight the critical functions of MST1 in B cell development, but also demonstrate its role in maintaining immune tolerance to prevent B cell overactivation through the regulation of CD4 + T cells.…”

Section: Hippo Pathway In Adaptive Immune Cell Lineage and Functionsmentioning

confidence: 99%

Hippo Pathway in Mammalian Adaptive Immune System

Yamauchi

Moroishi

2019

Cells

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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.

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“…This biased differentiation may create an IL-4-rich environment which contributes to the activation, proliferation, and differentiation of plasmacytes, accounting for the hypergammaglobulinemia of Mst1 −/− mice. Indeed, Mst1 −/− naïve T cells can promote the activation of B cells and plasma cell differentiation, resulting in a higher serum level of IgG, IgA and IgE ( 66 ). CD40-CD40L interactions on respective B cells and T cells provide a crucial second signal for B cell activation; however, Mst −/− CD4 + T cells do not express aberrant levels of CD40L.…”

Section: Mst1 and T Cell Differentiationmentioning

confidence: 99%

The Role of Mst1 in Lymphocyte Homeostasis and Function

et al. 2018

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The Hippo pathway is an evolutionarily conserved pathway crucial for regulating tissue size and for limiting cancer development. However, recent work has also uncovered key roles for the mammalian Hippo kinases, Mst1/2, in driving appropriate immune responses by directing T cell migration, morphology, survival, differentiation, and activation. In this review, we discuss the classical signaling pathways orchestrated by the Hippo signaling pathway, and describe how Mst1/2 direct T cell function by mechanisms not seeming to involve the classical Hippo pathway. We also discuss why Mst1/2 might have different functions within organ systems and the immune system. Overall, understanding how Mst1/2 transmit signals to discrete biological processes in different cell types might allow for the development of better drug therapies for the treatments of cancers and immune-related diseases.

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MST1 deficiency promotes B cell responses by CD4 + T cell-derived IL-4, resulting in hypergammaglobulinemia

Cited by 14 publications

References 16 publications

The Hippo Pathway: Immunity and Cancer

The Hippo Pathway: Immunity and Cancer

Hippo Pathway in Mammalian Adaptive Immune System

The Role of Mst1 in Lymphocyte Homeostasis and Function

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