Human MIKO-1, a Hybrid Protein That Regulates Macrophage Function, Suppresses Lung Fibrosis in a Mouse Model of Bleomycin-Induced Interstitial Lung Disease

Although interstitial lung disease (ILD) is a life-threatening pathological condition that causes respiratory failure, the efficiency of current therapies is limited. This study aimed to investigate the effects of human MIKO-1 (hMIKO-1), a hybrid protein that suppresses the abnormal activation of macrophages, on murine macrophage function and its therapeutic effect in a mouse model of bleomycin-induced ILD (BLM-ILD). To this end, the phenotype of thioglycolate-induced murine peritoneal macrophages co-cultured with hMIKO-1 was examined. The mice were assigned to normal, BLM-alone, or BLM + hMIKO-1 groups, and hMIKO-1 (0.1 mg/mouse) was administered intraperitoneally from day 0 to 14. The mice were sacrificed on day 28, and their lungs were evaluated by histological examination, collagen content, and gene expression levels. hMIKO-1 suppressed the polarization of murine macrophages to M2 predominance in vitro. The fibrosis score of lung pathology and lung collagen content of the BLM + hMIKO-1 group were significantly lower than those in the BLM-alone group. The expression levels of TNF-α, IL-6, IL-1β, F4/80, and TIMP-1 in the lungs of the BLM + hMIKO-1 group were significantly lower than those in the BLM-alone group. These findings indicate that hMIKO-1 reduces lung fibrosis and may be a future therapeutic candidate for ILD treatment

Polymorphisms and expression of toll-like receptors in autoimmune thyroid diseases

Graves’ disease (GD) and Hashimoto’s disease (HD) are autoimmune thyroid diseases (AITDs). Prognosis of AITDs varies in each patient. Toll-like receptors (TLRs) are pattern-recognition receptors that activate signaling pathways involved in the production of proinflammatory cytokines. UNC93B1 is a transcription factor of TLR7 and TLR9. In this study, we examined the association of TLR expression and TLR and UNC93B1 polymorphisms with the development and prognosis of AITDs. The ratio of intracellular TLR7 (iTLR7) and iTLR9 intensities in B cells was lower in patients with GD in remission than in patients with intractable GD (p = 0.0007). The frequency of G allele of TLR7 rs3853839 G/C polymorphism was significantly higher in male patients with GD and intractable GD than in control subjects (p = 0.0062 and 0.0173, respectively). The frequencies of T allele of TLR9 rs187084 C/T polymorphism and C allele of TLR9 rs352140 C/T polymorphism were significantly higher in patients with intractable GD who had GG genotype of TLR7 rs3853839 polymorphism, which is associated with higher TLR7 expression, than in patients with GD in remission (p = 0.0334 and 0.0023, respectively). The frequencies of AA genotype and A allele of UNC93B1 rs308328 polymorphism were significantly higher in patients with GD than in patients with HD (p = 0.0406 and 0.0316, respectively). These results suggested that the ratio of iTLR7 and iTLR9 intensities was associated with the development and intractability of GD and that TLR7 and UNC93B1 polymorphisms were associated with the development of GD

Increased Serum LIGHT Levels Correlate with Disease Progression and Severity of Interstitial Pneumonia in Patients with Dermatomyositis: A Case Control Study.

Activated CD8+ T cells play an important role in the pathogenesis of dermatomyositis (DM) with interstitial pneumonia (IP). Serum CD8+ T-cell activator, LIGHT, and Th1/Th2/Th17 cytokines were measured in DM-IP patients and compared with clinical parameters to investigate their usefulness.The correlations between the clinical findings and serum LIGHT and Th1/Th2/Th17 cytokine levels were investigated in 21 patients with DM-IP (14 with rapidly progressive IP [RPIP] and 7 with chronic IP [CIP], including 4 fatal cases of IP).The median serum LIGHT level was 119 (16-335.4) pg/ml, which was higher than that in healthy control subjects and DM patients without IP. The median serum IL-6 level was 14.7 (2.4-154.5) pg/ml (n = 13). The other cytokines were detected in only a few patients. The median serum LIGHT level in DM-RPIP patients (156 [49.6-335.4] pg/ml) was significantly higher than that in DM-CIP patients (94.3 [16-164.2] pg/ml) (P = 0.02). The serum IL-6 level did not correlate with either progression or outcome of DM-IP. ROC curve analysis determined a serum LIGHT level of ≥120 pg/ml to be the cut-off value for the rapid progression of DM-IP. Serum LIGHT levels correlated significantly with %DLco (R = 0.55, P = 0.04) and total ground-glass opacity scores (R = 0.72, P = 0.0002). The serum LIGHT level significantly decreased to 100.5 (12.4-259.3) pg/ml 4 weeks after treatment initiation (P = 0.04).The serum LIGHT level may be a promising marker of disease progression and severity in patients with DM-IP