No abstract

Using our diagnostic criteria, we could recruit relatively many patients with similar characteristics to those of idiopathic PPFE patients in the literature. The possibility of clinical diagnosis of idiopathic PPFE should be further discussed.

d Tuberculosis (TB) continues to be a major health problem, and there are few biomarkers for predicting prognosis. Indoleamine 2,3-dioxygenase (IDO), a potent immunoregulatory molecule, catalyzes the rate-limiting step of tryptophan (Trp) degradation in the kynurenine (Kyn) pathway. An increase in IDO activity determined by the serum Trp/Kyn ratio has been shown to be associated with poor prognosis in cancers and bacteremia. In TB, however, there are no studies measuring serum IDO activity to determine its clinical significance. We evaluated serum IDO activity with 174 pulmonary TB (PTB) patients and 85 controls, using liquid chromatography/electrospray ionization tandem mass spectrometry. IDO activity was estimated by calculating the serum Kyn-to-Trp ratio. PTB patients had significantly higher Kyn concentrations and IDO activity and significantly lower Trp concentrations (P < 0.0001, P < 0.0001, and P < 0.0001, respectively) than the controls. Of 174 PTB patients, 39 (22.4%) died. The patients who died had significantly higher concentrations of Kyn and significantly lower Trp concentrations, resulting in significantly higher IDO activity (P < 0.0001, P < 0.0001, and P < 0.0001, respectively). In a receiver operating characteristic (ROC) analysis, serum IDO activity had the highest area under the curve (0.850), and this activity was an independent prognostic factor in multivariate analysis. These results suggest that serum IDO activity can be used as a novel prognostic marker in PTB.T uberculosis (TB) remains a worldwide health problem, with 8.8 million new cases per year (21, 24). Advanced diagnosis technique, such as PCR for TB DNA and gamma interferon (IFN-␥) release assays (IGRAs), have improved detection of TB, and progress in multidrug combination therapy and expansion of directly observed therapy (DOTS) has increased the treatment completion rate and reduced the relapse rate. However, TB still causes over 1.6 million deaths per year (21,24). To assess the disease activity, therapeutic response, or risk for relapse, a large number of candidate biomarkers, such as sputum microbiologic examinations, serum neopterin, IGRAs, and urine tuberculous DNA, have been vigorously investigated (18, 21). However, there are few useful markers for predicting mortality in pulmonary TB (PTB).Indoleamine 2, 3-dioxygenase (IDO) is the rate-limiting enzyme that catalyzes tryptophan (Trp) degradation along the kynurenine (Kyn) pathway (9,11,12,19,25). In infectious diseases, IDO was initially considered an antimicrobial molecule acting through local starvation of Trp, which is an essential amino acid for bacterial growth. Interestingly, recent studies have unveiled a novel immunoregulatory role of IDO. By reducing the local Trp concentration and producing immunomodulatory Trp metabolites, such as Kyn, IDO potently inhibits T-cell functions and generates regulatory T cells (Treg), leading to immune suppression or tolerance. More interestingly, this immunoregulatory role of IDO has been shown to be associated with the immune esc...

Mouse lung dendritic cells (LDCs) have been recently shown to contain two major subpopulations: CD103(+) CD11b(low or negative) (CD103(+) LDCs) and CD103(-) CD11b(high) LDCs (CD11b(high) LDCs). Although several studies have demonstrated functional differences between them, it is unclear whether the subpopulations induce distinct T helper (Th) cell responses. The present study was conducted to examine whether CD103(+) and CD11b(high) LDCs preferentially generate different Th responses. Naive DO11.10 CD4(+) T cells were primed with CD103(+) or CD11b(high) LDCs obtained from normal BALB/c mice. The primed CD4(+) T cells were restimulated, and their cytokine secretions were assessed. The expression of intracellular cytokines and the mRNA levels of chemokine receptors were also measured. We found that the CD4(+) T cells primed with CD103(+) LDCs secreted significantly larger amounts of IFN-γ and IL-17A, whereas those primed with CD11b(high) LDCs released significantly higher levels of IL-4, IL-6, and IL-10. Intracellular cytokine assay showed that CD103(+) LDCs induced greater frequencies of CD4(+) T cells producing IFN-γ and IL-17A, whereas CD11b(high) LDCs were more efficient at inducing CD4(+) T cells producing IL-4 and IL-10. The mRNA levels of CXCR3 and CCR5, which are expressed preferentially in Th1 cells, were significantly higher in CD4(+) T cells primed with CD103(+) LDCs. The mRNA levels of CXCR4 and CCR4, which are expressed primarily in Th2 cells, were significantly greater in those primed with CD11b(high) LDCs. These data suggest that mouse CD103(+) LDCs predominantly elicit Th1 and Th17 responses, whereas CD11b(high) LDCs primarily provoke a Th2 response under the steady state.

These data suggest that YKL-40 is increased in the circulation and lungs of IPF patients, suggesting that this glycoprotein is associated with the pathophysiology of IPF.