Oral-Nasopharyngeal Dendritic Cells Mediate T Cell-Independent IgA Class Switching on B-1 B Cells

Native cholera toxin (nCT) as a nasal adjuvant was shown to elicit increased levels of T-independent S-IgA antibody (Ab) responses through IL-5- IL-5 receptor interactions between CD4+ T cells and IgA+ B-1 B cells in murine submandibular glands (SMGs) and nasal passages (NPs). Here, we further investigate whether oral-nasopharyngeal dendritic cells (DCs) play a central role in the induction of B-1 B cell IgA class switch recombination (CSR) for the enhancement of T cell-independent (TI) mucosal S-IgA Ab responses. High expression levels of activation-induced cytidine deaminase, Iα-Cμ circulation transcripts and Iμ-Cα transcripts were seen on B-1 B cells purified from SMGs and NPs of both TCRβ−/− mice and wild-type mice given nasal trinitrophenyl (TNP)-LPS plus nCT, than in the same tissues of mice given nCT or TNP-LPS alone. Further, DCs from SMGs, NPs and NALT of mice given nasal TNP-LPS plus nCT expressed significantly higher levels of a proliferation-inducing ligand (APRIL) than those in mice given TNP-LPS or nCT alone, whereas the B-1 B cells in SMGs and NPs showed elevated levels of transmembrane activator and calcium modulator cyclophilin ligand interactor (TACI) expression. Interestingly, high frequencies of IgA+ B-1 B cells were induced when peritoneal IgA− IgM+ B cells were stimulated with mucosal DCs from mice given nasal TNP-LPS plus nCT. Taken together, these findings show that nasal nCT plays a key role in the enhancement of mucosal DC-mediated TI IgA CSR by B-1 B cells through their interactions with APRIL and TACI

CANGAROO-III observation of TeV gamma rays from the unidentified gamma-ray source HESS J1614-518

We report the detection, with the CANGAROO-III imaging atmospheric Cherenkov telescope array, of a very high energy gamma-ray signal from the unidentified gamma-ray source HESS J1614-518, which was discovered in the H.E.S.S. Galactic plane survey. Diffuse gamma-ray emission was detected above 760 GeV at the 8.9 sigma level during an effective exposure of 54 hr from 2008 May to August. The spectrum can be represented by a power-law: 8.2+-2.2_{stat}+-2.5_{sys}x10^{-12}x (E/1TeV)^{-Gamma} cm^{-2} s^{-1} TeV^{-1} with a photon index Gamma of 2.4+-0.3_{stat}+-0.2_{sys}, which is compatible with that of the H.E.S.S. observations. By combining our result with multi-wavelength data, we discuss the possible counterparts for HESS J1614-518 and consider radiation mechanisms based on hadronic and leptonic processes for a supernova remnant, stellar winds from massive stars, and a pulsar wind nebula. Although a leptonic origin from a pulsar wind nebula driven by an unknown pulsar remains possible, hadronic-origin emission from an unknown supernova remnant is preferred.Comment: 9 pages, 7 figures, accepted for publication in Ap

Functional transforming growth factor-β receptor type II expression by CD4+ T cells in Peyer's patches is essential for oral tolerance induction.

Our previous studies have shown that Peyer's patches (PPs) play a key role in the induction of oral tolerance. Therefore, we hypothesized that PPs are an important site for Transforming Growth Factor (TGF)-β signaling and sought to prove that this tissue is of importance in oral tolerance induction. We found that expression of TGF-β type II receptor (TGFβRII) by CD4(+) T cells increases and persists in the PPs of normal C57BL/6 mice after either high- or low-dose feeding of OVA when compared to mesenteric lymph nodes (MLNs) and spleen. Approximately one-third of these TGFβRII(+) CD4(+) T cells express the transcription factor Foxp3. Interestingly, the number of TGFβRII(+) CD4(+) T cells in PPs decreased when OVA-fed mice were orally challenged with OVA plus native cholera toxin (CT). In contrast, numbers of TGFβRII(+) CD4(+) T cells were increased in the intestinal lamina propria (iLP) of these challenged mice. Further, these PP CD4(+) TGFβRII(+) T cells upregulated Foxp3 within 2 hours after OVA plus CT challenge. Mice fed PBS and challenged with OVA plus CT did not reveal any changes in TGFβRII expression by CD4(+) T cells. In order to test the functional property of TGFβRII in the induction of oral tolerance, CD4dnTGFβRII transgenic mice, in which TGFβRII signaling is abrogated from all CD4(+) T cells, were employed. Importantly, these mice could not develop oral tolerance to OVA. Our studies show a critical, dose-independent, role for TGFβRII expression and function by CD4(+) T cells in the gut-associated lymphoid tissues, further underlining the vital role of PPs in oral tolerance

Association between Dietary Habit and Clinical Parameters in Patients with Chronic Periodontitis Undergoing Supportive Periodontal Therapy

The recurrence risk evaluation has been emphasized in periodontal stabilization during supportive periodontal therapy (SPT). However, nutritional factors, e.g., dietary habits such as the frequency of eating vegetables, are rarely included in the evaluation. In this study, the effect of nutritional factors on clinical periodontal parameters was examined in a lifestyle-related investigation and a periodontal examination in patients with periodontitis undergoing SPT. A total of 106 patients were recruited. Tendencies toward a negative correlation were found between rate of a probing depth (PD) of 4–5 mm, rate of PD ≥ 6 mm, the bleeding on probing (BOP) rate, periodontal inflamed surface area (PISA), and various nutritional factors. The number of teeth was a clinical parameter with a significantly high R2 (≥0.10) influenced by environmental factors, whereas PD, PD of 4–5 mm, the BOP rate, and PISA were influenced by nutritional factors. These results suggested that environmental factors reflected clinical parameters showing long-term pathophysiology, such as the PD rate. Nutritional factors tended to affect the current inflammatory pathophysiology, such as the BOP rate, PISA, and PISA/periodontal epithelial surface area. Therefore, environmental and nutritional factors appear to be useful for evaluating the risk of periodontitis during SPT

Identification of Nutritional Factors to Evaluate Periodontal Clinical Parameters in Patients with Systemic Diseases

Nutritional factors reflect the periodontal parameters accompanying periodontal status. In this study, the associations between nutritional factors, blood biochemical items, and clinical parameters were examined in patients with systemic diseases. The study participants were 94 patients with heart disease, dyslipidemia, kidney disease, or diabetes mellitus. Weak negative correlation coefficients were found between nine clinical parameters and ten nutritional factors. Stage, grade, mean probing depth (PD), rate of PD 4–5 mm, rate of PD ≥ 6 mm, mean clinical attachment level (CAL), and the bleeding on probing (BOP) rate were weakly correlated with various nutritional factors. The clinical parameters with coefficients of determinations (R2) > 0.1 were grade, number of teeth, PD, rate of PD 4–5 mm, CAL, and BOP rate. PD was explained by yogurt and cabbage with statistically significant standardized partial regression coefficients (yogurt: −0.2143; cabbage and napa cabbage: −0.2724). The mean CAL was explained by pork, beef, mutton, and dark green vegetables with statistically significant standardized partial regression coefficients (−0.2237 for pork, beef, and mutton; −0.2667 for dark green vegetables). These results raise the possibility that the frequency of intake of various vegetables can be used to evaluate periodontal stabilization in patients with systemic diseases