Background Microgravity directly disturbs the reorganization of the cytoskeleton, exerting profound effects on the physiological process of macrophages. Although it has been established that macrophage M1/M2 polarization could be manipulated by the surface nanostructure of biomaterial in our previous study under normal gravity, how will inflammatory monocytes (iMos)-derived macrophages respond to diverse nanostructured Ti surfaces under normal gravity or microgravity remains unrevealed. Results In this study, Cytochalasin D, a cytoskeleton relaxant, was employed to establish the simulated microgravity (SMG) environment. Our results showed that human iMos polarized into M2c macrophages on NT5 surface but M1 type on NT20 surface with divergent inflammatory phenotypes according to the profile of macrophage polarization featured molecules under normal gravity. However, such manipulative effects of NTs surfaces on iMos-derived macrophages were strikingly weakened by SMG, characterized by the altered macrophage morphology, changed cytokine secretion profile, and decreased cell polarization capacity. Conclusions To our knowledge, this is the first metallic implantable material study focusing on the functions of specific monocyte subsets and its crucial role of the cytoskeleton in materials-mediated host immune response, which enriches our mechanism knowledge about the crosstalk between immunocytes and biomaterials. The results obtained in the present study may also provide potential targets and strategies for biomaterial development and clinical treatment via precise immune-regulation under normal gravity and microgravity. Graphic Abstract

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Diabetic cardiomyopathy (DCM) is one of the main complications in type I diabetic patients. Activated macrophage is critical for directing the process of inflammation during the development of DCM. The present study focused on the roles of CD226 on macrophage function during the DCM progression. It has been found that the number of cardiac macrophages in the hearts of streptozocin (STZ)‐induced diabetes mice was significantly increased compared with that in non‐diabetes mice, and the expression level of CD226 on cardiac macrophages in STZ‐induced diabetes mice was higher than that in non‐diabetes mice. CD226 deficiency attenuated the diabetes‐induced cardiac dysfunction and decreased the proportion of CD86+F4/80+ macrophages in the diabetic hearts. Notably, adoptive transfer of Cd226−/−‐ bone marrow derived macrophages (BMDMs) alleviated diabetes‐induced cardiac dysfunction, which may be due to the attenuated migration capacity of Cd226−/−‐BMDM under high glucose stimulation. Furthermore, CD226 deficiency decreased the macrophage glycolysis accompanying by the downregulated hexokinase 2 (HK2) and lactate dehydrogenase A (LDH‐A) expression. Taken together, these findings revealed the pathogenic roles of CD226 played in the process of DCM and provided a basis for the treatment of DCM.

Background Hantaan virus (HTNV) infection can cause severe hemorrhagic fever with renal syndrome (HFRS). Inflammatory monocytes (iMOs) are involved in early antiviral responses. Previous studies have found that blood iMOs numbers increase in the acute phase of HFRS. Here, we further identified the phenotypic characteristics of iMOs in HFRS and explored whether phenotypic changes in iMOs were associated with HFRS severity. Materials and Methods Blood samples from 85 HFRS patients were used for phenotypic analysis of iMOs by flow cytometry. Plasma HTNV load was determined using RT-PCR. THP-1 cells overexpressing CD226 were used to investigate the effects of CD226 on HLA-DR/DP/DQ and CD80 expression. A mouse model was used to test macrophage phenotype following HTNV infection. Results The proportion of CD226 - iMOs in the acute phase of HFRS was 66.83 (35.05-81.72) %, which was significantly higher than that in the convalescent phase (5.32 (1.36-13.52) %) and normal controls (7.39 (1.15-18.11) %) ( p < 0.0001). In the acute phase, the proportion of CD226 - iMOs increased more in patients with more severe HFRS and correlated positively with HTNV load and negatively with platelet count. Notably, CD226 - iMOs expressed lower levels of HLA-DR/DP/DQ and CD80 than CD226 + iMOs, and overexpression CD226 could enhance the expression of HLA-DR/DP/DQ and CD80. In a mouse model, HTNV also induced the expansion of CD226 - macrophages, with decreased expression of I-A/I-E and CD80. Conclusions CD226 - iMOs increased during HTNV infection and the decrease in CD226 hampered the expression of HLA-DR/DP/DQ and CD80, which may promote the immune escape of HTNV and exacerbate clinical symptoms.

It has been found that CD226 plays an important role in regulating macrophage function, but its expression and function on macrophage during renal fibrogenesis have not been studied. Our data demonstrated that CD226 expression in macrophages was obviously upregulated in the UUO model, while CD226 deficiency attenuated collagen deposition in renal inerestitum along with fewer number of M1 within renal cortex and renal medulla and a lower level of proinflammatory factors compared to control littermates. Further studies demonstrated that Cd226-/–BMDMs transferring to Cd226+/+ mice could significantly reduce the tubular injury, collagen deposition and proinflammatory cytokines secretion compared with WT-BMDMs group and WT-PBS group in adoptively transferring assay. Mechanistic investigations revealed that CD226 could suppress KLF4 expression in macrophages, which subsequently promoted more proinflammatory M1 accumulation in the kidney of WT mice than that of CD226 deficient mice. In vitro, we silenced KLF4 expression in BMDMs deriving from WT or CD226 deficient mice and the trend that CD226 promting more numbers of M1 disappeared. Therefore, our results uncover a pathogenic role of CD226 during the development of CKD by promoting monocyte infiltration from peripheral blood into the kidney and enhancing macrophage activation towards to the inflammatory phenotype by suppressing KLF4 expression.