CD11c regulates neutrophil maturation

Abstract

Neutrophils are the first-line defense immune cells against invading microbes. The bone marrow releases mature neutrophils into a circulation on a regular basis. In sepsis and other severe infections, a significant number of neutrophils is required, leading into an accelerated production of neutrophils when immature neutrophils are also released to meet a demand in these settings despite their less effective functions for microbial eradication. Here, we discovered that CD11c was expressed in neutrophils, and regulated neutrophil maturation and effector functions. In the absence of CD11c, neutrophil maturation was impaired in the bone marrow, associated with a significant increase in proliferation and apoptosis of pre-neutrophils. Inadequate neutrophil maturation was complicated with less effector functions. This phenotype was recapitulated in HL-60 differentiated neutrophils devoid of CD11c, supporting the idea of CD11c-driven intrinsic regulation of neutrophil maturation. In a lipopolysaccharide challenge to induce an emergent neutrophil production in the bone marrow, the deficiency of CD11c exaggerated the release of immature neutrophils into a circulation, associated with a significant proliferation and apoptosis of pre-neutrophils. In contrast, the constitutively active CD11c knock-in mouse showed accelerated neutrophil maturation and enhanced effector functions. Furthermore, the constitutively active CD11c knock-in mice offered enhanced bacterial eradication. Finally, we discovered that IQGAP1 interacted with CD11c. Deficiency of IQGAP1 largely impaired their maturation and effector functions associated with higher apoptosis under neutrophil differentiation stimulants. Taken together, we discovered that CD11c was critical for the regulation of neutrophil maturation via interacting with IQGAP1 and considered a potential target for sepsis treatment.

Integrin CD11c regulates B cell homeostasis

“…We previously showed that CD11c plays a role in proliferation and apoptosis of developing neutrophils ( 3 ). Therefore, we assessed if proliferation and apoptosis was also involved in the maintenance of BM and splenic B cells in the presence or absence of CD11c.…”

“…Bone marrow (BM) cells were obtained and cultured in 6 well plates in RPMI1640 supplemented with 10% heat inactivated FBS, glutamine, penicillin, streptomycin, GM-CSF (20 ng/mL) and IL-4 (5 ng/mL). At day 3, the culture medium was entirely discarded and replaced with freshly warmed medium containing GM-CSF and IL-4 ( 3 ). At day 7, part of cells was subjected to lipopolysaccharide (LPS) 10 µg/mL stimulation for 24 hours.…”

“…Although it is reported that it binds to iC3b, intercellular adhesion molecule-1 (ICAM-1) and fibrinogen in vitro ( 1 , 2 ), it is primarily known as a dendritic cell marker in vivo . However, we recently reported that CD11c regulates neutrophil maturation and T cell development ( 3 , 4 ). Thus, it would be of great interest to examine if CD11c also affects other cell types.…”

Ocular surface immune transcriptome and tear cytokines in corneal infection patients

“…CD11c has also been shown to play a significant role in activating immune and inflammatory responses during P. aeruginosa infections, thus contributing to the defense against the pathogen ( Metruccio et al., 2017 ). Recent research on murine subjects has demonstrated that CD11c plays a significant role in regulating the neutrophil maturation process and its associated effector functions ( Hou et al., 2023 ). In a mouse study on P. aeruginosa corneal infections, initiating apoptosis of neutrophils at an earlier stage resulted in better disease outcomes ( Zhou et al., 2008 ).…”

METTL3‐mediated N6‐methyladenosine exacerbates ferroptosis via m6A‐IGF2BP2‐dependent mitochondrial metabolic reprogramming in sepsis‐induced acute lung injury

“…An uncontrolled inflammatory response and endothelial barrier dysfunction characterise sepsis and ALI/ARDS 9,10 . During the progression of the disease, polymorphonuclear neutrophils (PMNs) are the first line of immune defence against pathogens 11 . In addition to their well‐known defence mechanisms, such as phagocytosis and degranulation, neutrophils can release neutrophil extracellular traps (NETs)—webs of DNA material decorated with bactericidal proteins—to efficiently ensnare microorganisms in the circulation 12 .…”