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Background: CD34 is a transmembrane phosphoglycoprotein and a marker of hematopoietic and nonhematopoietic stem/progenitor cells. In experimental studies, CD34+ cells are rich sources of endothelial progenitor cells and can promote neovascularization and endothelial repair. The potential role of CD34+ cells in stroke patients remains unclear. Aims: We aimed to assess the prognostic effect of circulating CD34+ cell levels on the risk of vascular events and functional prognosis in stroke patients. Patients and methods: In this prospective observational study, patients with ischemic stroke were consecutively enrolled within 1 week of onset and followed up for 1 year. Patients were divided into three groups according to tertiles of the level of circulating CD34+ cells (Tertile 1, <0.51/µL; Tertile 2, 0.51–0.96/µL; and Tertile 3, >0.96/µL). The primary outcome was a composite of major adverse cardiovascular events (MACEs), including nonfatal stroke, nonfatal acute coronary syndrome, major peripheral artery disease, and vascular death. The secondary outcomes included the modified Rankin scale (mRS) scores. Results: A total of 524 patients (mean age, 71.3 years; male, 60.1%) were included. High CD34+ cell levels were associated with younger age (p < 0.001) and low National Institutes of Health Stroke Scale scores at admission (p = 0.010). No significant differences were found in the risk of MACEs among the three groups (annual rates: 15.0%, 13.4%, and 12.6% in Tertiles 1, 2, and 3, respectively; log-rank p = 0.70). However, there were significant differences in the mRS scores at 3 months (median (interquartile range); 2 (1–4), 1 (1–3), and 1 (0–2) in Tertiles 1, 2, and 3, respectively; p = 0.010) and 1 year (3 (1–4), 2 (1–4), and 1 (0–3); p < 0.001) among these groups. After multivariable adjustments, a higher CD34+ cell level was independently associated with good functional outcomes (mRS score of 0–2) at 3 months (adjusted odds ratio (OR), 1.43; 95% confidence interval (CI), 1.01–2.05) and 1 year (adjusted OR, 1.53; 95% CI, 1.09–2.16). Conclusion: Although no correlations were found between circulating CD34+ cell levels and vascular event risk, elevated CD34+ cell levels were associated with favorable functional recovery in stroke patients. Data access statement: Data supporting the findings of this study are available from the corresponding author on reasonable request. Clinical trial registration: The TWMU Stroke Registry is registered at https://upload.umin.ac.jp as UMIN000031913. [ABSTRACT FROM AUTHOR]

Macrophages are professional phagocytic cells that orchestrate innate immune responses and have considerable phenotypic diversity at different anatomical locations. However, the mechanisms that control the heterogeneity of tissue macrophages are not well characterized. Here we found that the nuclear receptor LXRα was essential for the differentiation of macrophages in the marginal zone (MZ) of the spleen. LXR-deficient mice were defective in the generation of MZ and metallophilic macrophages, which resulted in abnormal responses to blood-borne antigens. Myeloid-specific expression of LXRα or adoptive transfer of wild-type monocytes restored the MZ microenvironment in LXRα-deficient mice. Our results demonstrate that signaling via LXRα in myeloid cells is crucial for the generation of splenic MZ macrophages and identify an unprecedented role for a nuclear receptor in the generation of specialized macrophage subsets.

Acute kidney injury (AKI) is associated with prolonged hospitalization and high mortality, and it predisposes individuals to chronic kidney disease. To date, no effective AKI treatments have been established. Here we show that the apoptosis inhibitor of macrophage (AIM) protein on intraluminal debris interacts with kidney injury molecule (KIM)-1 and promotes recovery from AKI. During AKI, the concentration of AIM increases in the urine, and AIM accumulates on necrotic cell debris within the kidney proximal tubules. The AIM present in this cellular debris binds to KIM-1, which is expressed on injured tubular epithelial cells, and enhances the phagocytic removal of the debris by the epithelial cells, thus contributing to kidney tissue repair. When subjected to ischemia-reperfusion (IR)-induced AKI, AIM-deficient mice exhibited abrogated debris clearance and persistent renal inflammation, resulting in higher mortality than wild-type (WT) mice due to progressive renal dysfunction. Treatment of mice with IR-induced AKI using recombinant AIM resulted in the removal of the debris, thereby ameliorating renal pathology. We observed this effect in both AIM-deficient and WT mice, but not in KIM-1-deficient mice. Our findings provide a basis for the development of potentially novel therapies for AKI., AKI is characterized by impaired kidney-filtration function, caused by insults such as kidney ischemia-reperfusion injury (IRI), sepsis or nephrotoxins. Although most cases of AKI are reversible, it is believed to [...]

During intrauterine life, the mammalian embryo survives via its physical connection to the mother. The uterine decidua, which differentiates from stromal cells after implantation in a process known as decidualization, plays essential roles in supporting embryonic growth before establishment of the placenta. Here we show that female mice lacking death effector domain-containing protein (DEDD) are infertile owing to unsuccessful decidualization. In uteri of [Dedd.sup.-/-] mice, development of the decidual zone and the surrounding edema after embryonic implantation was defective. This was subsequently accompanied by disintegration of implantation site structure, leading to embryonic death before placentation. Polyploidization, a hallmark of mature decidual cells, was attenuated in DEDD-deficient cells during decidualization. Such inefficient decidualization appeared to be caused by decreased Akt levels, since polyploidization was restored in DEDD-deficient decidual cells by overexpression of Akt. In addition, we showed that DEDD associates with and stabilizes cyclin D3, an important element in polyploidization, and that overexpression of cyclin D3 in DEDD-deficient cells improved polyploidization. These results indicate that DEDD is indispensable for the establishment of an adequate uterine environment to support early pregnancy in mice., Introduction Approximately 10%-15% of couples experience infertility during their reproductive years, owing mainly to implantation failure. Among the reasons underlying such failure, defective development of functional decidua at the implantation [...]