miR-155: A Novel Target in Allergic Asthma

Zhou, Hong; Li, Junyao; Gao, Peng; Wang, Qi; Zhang, Jie

doi:10.3390/ijms17101773

Cited by 63 publications

(67 citation statements)

References 80 publications

(97 reference statements)

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“…Loss of SHIP protein is evident by 48 h poststimulation with IL‐4, SHIP protein levels continue to decline for 7 days, and SHIP protein levels are restored by 72 h after removal of the stimulus . Consistent with these observations, SHIP is a direct target of the well‐studied microRNA‐155 (miR‐155) and has been implicated as a possible target for the treatment of asthma and allergies . Together, these findings are consistent with a model in which SHIP acts as a critical negative regulator of type II inflammatory responses in innate immune cells.…”

Section: Shipsupporting

confidence: 80%

SHIP negatively regulates type II immune responses in mast cells and macrophages

Dobranowski

Sly

2018

Journal of Leukocyte Biology

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SHIP is a hematopoietic-specific lipid phosphatase that dephosphorylates PI3K-generated PI(3,4,5)-trisphosphate. SHIP removes this second messenger from the cell membrane blunting PI3K activity in immune cells. Thus, SHIP negatively regulates mast cell activation downstream of multiple receptors. SHIP has been referred to as the "gatekeeper" of mast cell degranulation as loss of SHIP dramatically increases degranulation or permits degranulation in response to normally inert stimuli. SHIP also negatively regulates Mϕ activation, including both pro-inflammatory cytokine production downstream of pattern recognition receptors, and alternative Mϕ activation by the type II cytokines, IL-4, and IL-13. In the SHIP-deficient (SHIP ) mouse, increased mast cell and Mϕ activation leads to spontaneous inflammatory pathology at mucosal sites, which is characterized by high levels of type II inflammatory cytokines. SHIP mast cells and Mϕs have both been implicated in driving inflammation in the SHIP mouse lung. SHIP Mϕs drive Crohn's disease-like intestinal inflammation and fibrosis, which is dependent on heightened responses to innate immune stimuli generating IL-1, and IL-4 inducing abundant arginase I. Both lung and gut pathology translate to human disease as low SHIP levels and activity have been associated with allergy and with Crohn's disease in people. In this review, we summarize seminal literature and recent advances that provide insight into SHIP's role in mast cells and Mϕs, the contribution of these cell types to pathology in the SHIP mouse, and describe how these findings translate to human disease and potential therapies.

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Section: Shipsupporting

confidence: 80%

SHIP negatively regulates type II immune responses in mast cells and macrophages

Dobranowski

Sly

2018

Journal of Leukocyte Biology

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“…27,28 In mouse models of asthma, miR-155 has been implicated in both the regulation of T H 2 cell differentiation and T H 2 cytokine production and might also play a part in mediating the effects of glucocorticoids. 29 …”

Section: Th2 Differentiation and T-cell Trafficking In Asthmatic Patimentioning

confidence: 99%

“…192,193 There is also interest in targeting miRNAs, such as miR-155; however, given that these molecules can exert differential effects at discrete stages of the T H 2 pathway, it is difficult to predict outcomes (Fig 6, C ). 29 Moreover, developing a pharmacologic strategy by which to deliver an anti-miRNA agent into cells in a specific stable manner will be a significant challenge.…”

Section: Future Directions and Clinical Implicationsmentioning

confidence: 99%

Pathogenic CD4 + T cells in patients with asthma

Muehling

Lawrence

Woodfolk

2017

Journal of Allergy and Clinical Immunology

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Asthma encompasses a variety of clinical phenotypes that involve distinct T cell–driven inflammatory processes. Improved understanding of human T-cell biology and the influence of innate cytokines on T-cell responses at the epithelial barrier has led to new asthma paradigms. This review captures recent knowledge on pathogenic CD4+ T cells in asthmatic patients by drawing on observations in mouse models and human disease. In patients with allergic asthma, TH2 cells promote IgE-mediated sensitization, airway hyperreactivity, and eosinophilia. Here we discuss recent discoveries in the myriad molecular pathways that govern the induction of TH2 differentiation and the critical role of GATA-3 in this process. We elaborate on how cross-talk between epithelial cells, dendritic cells, and innate lymphoid cells translates to T-cell outcomes, with an emphasis on the actions of thymic stromal lymphopoietin, IL-25, and IL-33 at the epithelial barrier. New concepts on how T-cell skewing and epitope specificity are shaped by multiple environmental cues integrated by dendritic cell “hubs” are discussed. We also describe advances in understanding the origins of atypical TH2 cells in asthmatic patients, the role of TH1 cells and other non-TH2 types in asthmatic patients, and the features of T-cell pathogenicity at the single-cell level. Progress in technologies that enable highly multiplexed profiling of markers within a single cell promise to overcome barriers to T-cell discovery in human asthmatic patients that could transform our understanding of disease. These developments, along with novel T cell–based therapies, position us to expand the assortment of molecular targets that could facilitate personalized treatments.

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“…Further study of miR‐155 function and its respective targets is also crucial and will provide a better understanding as to the molecular mechanisms underpinning autoimmune arthritis pathogenesis. Future research will investigate and identify the targeting genes of miR‐155 in different immune cells so as to facilitate the understanding of the molecular mechanisms of disease development and progression . This may help to relate miR‐155 expression to the altered expression of different protein‐coding genes in different immune responses.…”

Section: Resultsmentioning

confidence: 99%

“…Future research will investigate and identify the targeting genes of miR-155 in different immune cells so as to facilitate the understanding of the molecular mechanisms of disease development and progression. 43 This may help to relate miR-155 expression to the altered expression of different protein-coding genes in different immune responses. In addition, more studies should give new information regarding miR-155 expression and the altered expression of proteins, which can result in novel treatment strategies for this disease.…”

Section: Resultsmentioning

confidence: 99%

Role of microRNA‐155 in rheumatoid arthritis

Huang

Jia

et al. 2017

Int J of Rheum Dis

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MicroRNAs (miRNAs) are a recently discovered class of post-transcriptional regulators that induce target messenger RNA degradation or translation inhibition. miRNA-155 (miR-155) is an important regulator of immune cells both in humans and mice, by which these cells play critical roles in the pathogenesis of rheumatoid arthritis (RA). Recent findings showed that expression of miR-155 was elevated in RA patients and arthritis models. Moreover, miR-155 overexpression or knockdown performed significantly in the development of arthritis. This review summarizes the recent findings with respect to miR-155 in immune responses and the underlying mechanisms responsible for miR-155-related autoimmune arthritis. Hopefully the information obtained will benefit the development of novel therapeutic strategies.

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miR-155: A Novel Target in Allergic Asthma

Cited by 63 publications

References 80 publications

SHIP negatively regulates type II immune responses in mast cells and macrophages

SHIP negatively regulates type II immune responses in mast cells and macrophages

Pathogenic CD4 + T cells in patients with asthma

Role of microRNA‐155 in rheumatoid arthritis

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