TY - JOUR
T1 - β2 Integrin Signaling Cascade in Neutrophils: More Than a Single Function
AU - Bouti, Panagiota
AU - Webbers, Steven D. S.
AU - Fagerholm, Susanna C.
AU - Alon, Ronen
AU - Moser, Markus
AU - Matlung, Hanke L.
AU - Kuijpers, Taco W.
N1 - Funding Information: We are thankful to Sprenkeler Evelien for her help with the infographic. Publisher Copyright: © Copyright © 2021 Bouti, Webbers, Fagerholm, Alon, Moser, Matlung and Kuijpers.
PY - 2021/2/18
Y1 - 2021/2/18
N2 - Neutrophils are the most prevalent leukocytes in the human body. They have a pivotal role in the innate immune response against invading bacterial and fungal pathogens, while recent emerging evidence also demonstrates their role in cancer progression and anti-tumor responses. The efficient execution of many neutrophil effector responses requires the presence of β2 integrins, in particular CD11a/CD18 or CD11b/CD18 heterodimers. Although extensively studied at the molecular level, the exact signaling cascades downstream of β2 integrins still remain to be fully elucidated. In this review, we focus mainly on inside-out and outside-in signaling of these two β2 integrin members expressed on neutrophils and describe differences between various neutrophil stimuli with respect to integrin activation, integrin ligand binding, and the pertinent differences between mouse and human studies. Last, we discuss how integrin signaling studies could be used to explore the therapeutic potential of targeting β2 integrins and the intracellular signaling cascade in neutrophils in several, among other, inflammatory conditions in which neutrophil activity should be dampened to mitigate disease.
AB - Neutrophils are the most prevalent leukocytes in the human body. They have a pivotal role in the innate immune response against invading bacterial and fungal pathogens, while recent emerging evidence also demonstrates their role in cancer progression and anti-tumor responses. The efficient execution of many neutrophil effector responses requires the presence of β2 integrins, in particular CD11a/CD18 or CD11b/CD18 heterodimers. Although extensively studied at the molecular level, the exact signaling cascades downstream of β2 integrins still remain to be fully elucidated. In this review, we focus mainly on inside-out and outside-in signaling of these two β2 integrin members expressed on neutrophils and describe differences between various neutrophil stimuli with respect to integrin activation, integrin ligand binding, and the pertinent differences between mouse and human studies. Last, we discuss how integrin signaling studies could be used to explore the therapeutic potential of targeting β2 integrins and the intracellular signaling cascade in neutrophils in several, among other, inflammatory conditions in which neutrophil activity should be dampened to mitigate disease.
KW - CD11b/CD18 integrin
KW - neutrophil function
KW - neutrophils
KW - therapeutic targets
KW - β2 integrin signaling
UR - http://www.scopus.com/inward/record.url?scp=85102128296&partnerID=8YFLogxK
U2 - https://doi.org/10.3389/fimmu.2020.619925
DO - https://doi.org/10.3389/fimmu.2020.619925
M3 - Review article
C2 - 33679708
SN - 1664-3224
VL - 11
JO - Frontiers in immunology
JF - Frontiers in immunology
M1 - 619925
ER -