Asthma, a well-known helper T cell Type 2 (Th2)-mediated disease, has a polarized immune response toward a Th2 phenotype. However, the factors causing the Th2 polarization remain to be fully determined in this disease. Dendritic cells (DCs) are the most potent antigen-presenting cells that play a central role in initiating the primary immune response. In human blood, two functional distinct subsets of DCs, myeloid DCs and plasmacytoid DCs, have been identified. Myeloid DCs (mDCs) and plasmacytoid DCs (pDCs) are also called Type 1 DCs (DC1) and Type 2 DCs (DC2), respectively, because mDCs and pDCs were shown to preferentially differentiate naive T cells into Th1 and Th2 cells, respectively. In asthma, it can thus be speculated that an altered balance of mDCs to pDCs toward pDCs may contribute to the Th2 polarization. To clarify this, we examined the numbers of mDCs and pDCs in the peripheral blood of 44 patients with asthma and 38 normal subjects, using multicolor flow cytometry. We found that the patients with asthma had a significantly higher number of pDCs, resulting in a significant decrease in the ratio of mDCs to pDCs compared with normal subjects. These data indicate that the patients with asthma had a polarization of the mDC:pDC balance toward pDCs, which may be involved in producing the Th2-dominant immune phenotype in asthma.

Idiopathic NSIP included subjects who fulfilled the UCTD criteria, and these subjects had different clinical characteristics with significantly better outcome than those who did not meet the criteria. These data suggest that a part, but not all, of patients with idiopathic NSIP show CTD-like features with a distinct prognosis.

Background and objectiveRecent research has highlighted the fundamental role of sarcopenia, characterized by loss of skeletal muscle mass and strength, with a risk of poor outcomes. AFT preserves lung function by preventing the annual decline in FVC and is associated with improved outcomes in patients with IPF. However, altered cause of death and prognostic implications of sarcopenia in patients with IPF receiving AFT remain unknown.MethodsThis study comprised two cohorts of patients with IPF receiving AFT, historical cohort of IPF patients without AFT and controls. The cause of mortality was compared with a historical cohort. Sarcopenia was assessed by measuring the ESMCSA and ESMMA via CT.ResultsPatients with IPF had smaller ESMCSA and lower ESMMA but similar BMI than controls, suggesting patients with IPF had skeletal muscle loss without any obvious body weight loss. The most common cause of mortality in patients receiving AFT was chronic respiratory failure, accounting for approximately 60%, and decreased proportions of LC were found. Subsequently, low ESMCSA was an independent prognostic factor associated with worse survival rates. Furthermore, combined assessment of ESMCSA, %FVC predicted and BMI values provided clear prognostic distinction.ConclusionPatients with IPF receiving AFT showed skeletal muscle loss without obvious weight loss. These patients mostly died by chronic respiratory failure, and skeletal muscle wasting has prognostic significance, suggesting that preventing sarcopenia as well as preserving lung function are important for managing these patients.

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25-Hydroxyvitamin D(3)-1alpha-hydroxylase (1alpha-hydroxylase) plays a central role in calcium metabolism by synthesizing the active hormone 1alpha,25-dihydroxyvitamin D(3) in the kidney. Its increased expression in the extrarenal tissues has been found in alveolar macrophages in sarcoidosis but not in any other pathological conditions. We found that 1alpha-hydroxylase-mRNA in alveolar macrophages measured by semiquantitative RT-PCR was 2-fold greater in patients with lung cancer than in control subjects (0.61 +/- 0.20 vs. 0.34 +/- 0.11, respectively; P < 0.0001). When the clinical stages of lung cancer were divided into early (stage IA-IIIA) and advanced (stage IIIB and IV) and the expression of 1alpha-hydroxylase gene was compared among the control, early, and advanced groups, the advanced group showed the highest expression, followed by the early group, then the control group (0.34 +/- 0.11, 0.52 +/- 0.11, and 0.69 +/- 0.23 for control, early, and advanced groups, respectively; P < 0.0001). The 1alpha-hydroxylase-mRNA level was well correlated with serum 1alpha,25-dihydroxylase D(3) concentration and the 1alpha,25-dihydroxylase D(3) to 25-hydroxyvitamin D(3) ratio, but none of the findings related to calcium metabolism among the patients with lung cancer. Increased local production of 1alpha,25-dihydroxyvitamin D(3) may be associated with the pathological conditions, such as immunosuppression, in lung cancer.

CD206, a mannose receptor, is mainly expressed on the surface of alternatively activated macrophages where it acts as a pattern recognition receptor and plays a role in innate and adaptive immunity. This study investigated serum soluble CD206 (sCD206) levels in community-acquired pneumonia (CAP) and examined their clinical significance. sCD206 concentrations were measured in the sera of two independent cohorts with CAP (127 and 125 patients, respectively) and 42 controls. The expression of CD206 in the lung from autopsied cases was also examined. Patients with CAP showed significantly elevated sCD206 levels than did the controls (p < 0.0001). Notably, fatal CAP patients had more than two-fold higher sCD206 concentrations than survivors in both cohorts (p < 0.0001). Serum sCD206 concentrations were associated with Pneumonia Severity Index (PSI) and CURB-65 values. Importantly, even fatal CAP patients classified as PSI I-IV, CURB65 0–2 or age <75 years had comparatively higher levels of sCD206 than those classified as PSI V, CURB-65 3–5 or age ≥75 years. Immunohistochemically, the infiltration of CD206+ macrophages was found in the lungs of fatal cases. Elevated levels of sCD206 are associated with CAP prognosis, suggesting sCD206 might be a potential biomarker to predict severity for CAP.

Macrophage colony-stimulating factor (M-CSF) is a cytokine involved in the development and proliferation of the monocyte/macrophage lineage cells. M-CSF has also been reported to participate in the induction of osteoclasts, and may be important in the destruction of bone and cartilage and the periarticular osteoporotic changes seen in patients with rheumatoid arthritis (RA). We developed a new ELISA technique to measure M-CSF levels in synovial fluid with high sensitivity and reproducibility. The mean M-CSF level in the synovial fluid of patients with RA was 1.38 +/- 0.56 ng/ml, and that of patients with osteoarthritis (OA) was 0.67 +/- 0.13 ng/ml. In contrast, serum levels of M-CSF in patients with RA and in normal controls were 1.32 +/- 0.50 ng/ml and 0.90 +/- 0.09 ng/ml, respectively. These differences were both statistically significant. Since serum M-CSF levels correlate with inflammatory signs obtained from examination of blood, they indicate the general condition of patients with RA. Synovial fluid M-CSF levels increase even in the early phase of RA and remain high despite drug therapy, which suggests that they reflect the condition of affected joints including joint spaces and inflamed synovia more directly than do the levels of serum M-CSF. Measurement of the M-CSF level in the synovial fluid may be useful in the diagnosis, clinical evaluation, and assessment of the effects of treatment in patients with RA.