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The Activation and Regulation of β2 Integrins in Phagocytes and Phagocytosis

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FRONTIERS IN IMMUNOLOGY
卷 12, 期 -, 页码 -

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FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2021.633639

关键词

β 2 integrins; integrin activation; integrin adaptors; phagocytes; phagocytosis

资金

  1. National Institutes of Health, USA (NIH) [R01HL145454]
  2. UConn Health

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Phagocytes, such as neutrophils and macrophages, play a crucial role in protecting the body by removing foreign particles and dead cells. The activation of beta 2 integrins is essential for the recruitment and phagocytic function of these cells, but aberrant activation may exacerbate autoimmune diseases and tumor metastasis. Targeting beta 2 integrins to regulate phagocyte activities could benefit host defense functions with minimal side effects.
Phagocytes, which include neutrophils, monocytes, macrophages, and dendritic cells, protect the body by removing foreign particles, bacteria, and dead or dying cells. Phagocytic integrins are greatly involved in the recognition of and adhesion to specific antigens on cells and pathogens during phagocytosis as well as the recruitment of immune cells. beta 2 integrins, including alpha L beta 2, alpha M beta 2, alpha X beta 2, and alpha D beta 2, are the major integrins presented on the phagocyte surface. The activation of beta 2 integrins is essential to the recruitment and phagocytic function of these phagocytes and is critical for the regulation of inflammation and immune defense. However, aberrant activation of beta 2 integrins aggravates auto-immune diseases, such as psoriasis, arthritis, and multiple sclerosis, and facilitates tumor metastasis, making them double-edged swords as candidates for therapeutic intervention. Therefore, precise regulation of phagocyte activities by targeting beta 2 integrins should promote their host defense functions with minimal side effects on other cells. Here, we reviewed advances in the regulatory mechanisms underlying beta 2 integrin inside-out signaling, as well as the roles of beta 2 integrin activation in phagocyte functions.

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