CD11c regulates neutrophil maturation.

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.