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Recent studies have established that memory B cells, largely thought to be circulatory in the blood, can take up long-term residency in inflamed tissues, analogous to widely described tissue-resident T cells. The dynamics of recruitment and retention of memory B cells to tissues and their immunological purpose remains unclear. Here, we characterized tissue-resident memory B cells (BRM) that are stably maintained in the lungs of mice after pulmonary influenza infection. Influenza-specific BRM were localized within inducible bronchus-associated lymphoid tissues (iBALTs) and displayed transcriptional signatures distinct from classical memory B cells in the blood or spleen while showing partial overlap with memory B cells in lung-draining lymph nodes. We identified lung-resident markers, including elevated expression of CXCR3, CCR6, and CD69, on hemagglutinin (HA)– and nucleoprotein (NP)–specific lung BRM. We found that CCR6 facilitates increased recruitment and/or retention of BRM in lungs and differentiation into antibody-secreting cells upon recall. Although expression of CXCR3 and CCR6 was comparable in total and influenza-specific memory B cells isolated across tissues of human donors, CD69 expression was higher in memory B cells from lung and draining lymph nodes of human organ donors relative to splenic and PBMC-derived populations, indicating that mechanisms underpinning BRM localization may be evolutionarily conserved. Last, we demonstrate that human memory B cells in lungs are transcriptionally distinct to populations in lung-draining lymph nodes or PBMCs. These data suggest that BRM may constitute a discrete component of B cell immunity, positioned at the lung mucosa for rapid humoral response against respiratory viral infections. [ABSTRACT FROM AUTHOR]

Abstract Background Resveratrol is a natural polyphenolic compound known for its beneficial effects on energy homeostasis, and it also has multiple properties, including anti-oxidant, anti-inflammatory, and anti-tumor activities. Recently, silent information regulator genes (Sirtuins) have been identified as targets of resveratrol. Sirtuin 1 (SIRT1), originally found as an NAD+-dependent histone deacetylase, is a principal modulator of pathways downstream of calorie restriction, and the activation of SIRT1 ameliorates glucose homeostasis and insulin sensitivity. To date, the presence and physiological role of SIRT1 in the ovary are not known. Here we found that SIRT1 was localized in granulosa cells of the human ovary. Methods The physiological roles of resveratrol and SIRT1 in the ovary were analyzed. Immunohistochemistry was performed to localize the SIRT1 expression. SIRT1 protein expression of cultured cells and luteinized human granulosa cells was investigated by Western blot. Rat granulosa cells were obtained from diethylstilbestrol treated rats. The cells were treated with increasing doses of resveratrol, and subsequently harvested to determine mRNA levels and protein levels. Cell viability was tested by MTS assay. Cellular apoptosis was analyzed by caspase 3/7 activity test and Hoechst 33342 staining. Results SIRT1 protein was expressed in the human ovarian tissues and human luteinized granulosa cells. We demonstrated that resveratrol exhibited a potent concentration-dependent inhibition of rat granulosa cells viability. However, resveratrol-induced inhibition of rat granulosa cells viability is independent of apoptosis signal. Resveratrol increased mRNA levels of SIRT1, LH receptor, StAR, and P450 aromatase, while mRNA levels of FSH receptor remained unchanged. Western blot analysis was consistent with the results of quantitative real-time RT-PCR assay. In addition, progesterone secretion was induced by the treatment of resveratrol. Conclusions These results suggest a novel mechanism that resveratrol could enhance progesterone secretion and expression of luteinization-related genes in the ovary, and thus provide important implications to understand the mechanism of luteal phase deficiency.

Problem: Pre‐ovulatory mature follicles are not readily induced from gonadotropin (Gn)‐independent early follicles in the poor ovarian response (POR) state, characterized by reduced number of retrieved oocytes. Bone morphogenetic protein (BMP), which is expressed in the ovary, contributes to early folliculogenesis, but its precise underlying mechanism remains unknown. The purpose of this study was to examine the effects of BMP‐2 on granulosa cells (GCs) of Gn‐independent early follicles. Method of study: Sphingosine kinase 1 (SPHK1) localization, which produces sphingosine 1‐phosphate (S1P), was examined in human early follicles by immunohistochemistry. SPHK1 mRNA levels were examined in Gn‐independent bovine GCs (bGCs) and human nonluteinized granulosa cell line (HGrC1) cells. Phosphorylated Yes‐associated protein (YAP) expression was evaluated by Western blot, and its localization was evaluated immunocytochemically in bGCs. Verteporfin, a selective YAP inhibitor, was used to explore the influence of YAP on BMP‐2‐induced bGCs proliferation. Results: The expression of SPHK1 was observed in human GCs of primary and secondary follicles. BMP‐2 significantly induced SPHK1 mRNA expression in bGCs and HGrC1 cells. Both BMP‐2 and S1P decreased phosphorylated YAP protein levels and induced the nuclear translocation of YAP significantly, thereby increasing the number of bGCs by suppressing the Hippo pathway. This BMP‐2‐induced cell proliferation was completely blocked by verteporfin. Conclusion: This is a first report showing that BMP‐2 up‐regulated SPHK1 mRNA expression in GCs and promoted GCs proliferation through Hippo pathway suppression. Thus, BMP‐2 contributes to Gn‐independent folliculogenesis via SPHK1, suggesting a potential therapeutic strategy for the POR patients with follicular dysgenesis. [ABSTRACT FROM AUTHOR]

Objectives: Endemic human coronaviruses (hCoVs) circulate worldwide but cause minimal mortality. Although seroconversion to hCoV is near ubiquitous during childhood, little is known about hCoV‐specific T‐cell memory in adults. Methods: We quantified CD4 T‐cell and antibody responses to hCoV spike antigens in 42 SARS‐CoV‐2‐uninfected individuals. Antigen‐specific memory T cells and circulating T follicular helper (cTFH) cells were identified using an activation‐induced marker assay and characterised for memory phenotype and chemokine receptor expression. Results: T‐cell responses were widespread within conventional memory and cTFH compartments but did not correlate with IgG titres. SARS‐CoV‐2 cross‐reactive T cells were observed in 48% of participants and correlated with HKU1 memory. hCoV‐specific T cells exhibited a CCR6+ central memory phenotype in the blood, but were enriched for frequency and CXCR3 expression in human lung‐draining lymph nodes. Conclusion: Overall, hCoV‐specific humoral and cellular memory are independently maintained, with a shared phenotype existing among coronavirus‐specific CD4 T cells. This understanding of endemic coronavirus immunity provides insight into the homeostatic maintenance of immune responses that are likely to be critical components of protection against SARS‐CoV‐2. [ABSTRACT FROM AUTHOR]

Arcuate uterus does not impact the success of infertility treatments, but there is no consensus on whether it influences perinatal outcomes. The objective of the present study was to investigate whether minor congenital uterine anomalies such as an arcuate uterus contribute to perinatal complications. This was a retrospective cohort study at a single institution. The study included 1097 deliveries after 22 weeks of gestation. Transvaginal ultrasound, with three‐dimensional functionality, assessed uterine morphology based on American Society for Reproductive Medicine criteria. We compared maternal backgrounds and perinatal complications between arcuate uterus and normal uterus groups. Statistical analyses, including multivariate analysis, aimed to identify independent risk factors. A total of 69 patients (7.5%) with diagnosed arcuate uterus were included. Maternal background factors showed no significant differences between groups. In perinatal complications, an arcuate uterus was associated with a significantly higher incidence of preterm delivery (13% versus 4.7%, P = 0.01), preterm premature rupture of membranes (7.2% versus 1.6%, P = 0.01), fetal growth restriction (FGR; 16% versus 6.7%, P = 0.01), and abnormal placental cord insertion (33% versus 7.6%, P < 0.01). After multivariate analysis, arcuate uterus emerged as an independent risk factor for preterm delivery (adjusted odds ratio [aOR], 4.0 [95% confidence interval (CI), 1.6–9.9], P < 0.01), FGR (aOR, 2.6 [95% CI, 1.2–5.6], P = 0.02), and abnormal placental cord insertion (aOR, 6.0 [95% CI, 3.4–10.6], P < 0.01). Arcuate uterus stands as an independent risk factor for preterm delivery, FGR, and abnormal placental cord insertion. The findings emphasize the importance of recognizing even minor uterine morphological abnormalities in assessing and managing perinatal complications. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study was to investigate the efficacy of T2 star (T2*) mapping in diagnosing ovarian cysts/ tumors. Methods: Pelvic magnetic resonance examinations including T2*WI were performed before surgery in 35 patients. The region of interest, consisted of a 10 mm2 diameter circle, was set as much as possible inside ovarian tumors/cysts to measure T2*values, and mean T2* values were compared in ovarian cyst/tumor types, retrospectively. Diagnoses of 40 ovarian cysts/tumors were determined by pathological reports, in which 17 were endometriomas, 13 were mature cystic teratomas, 6 were mucinous cystadenomas and 4 were serous cystadenomas. Results: The average T2* values of endometrioma was 56.8 ± 8.7 ms (mean ± SEM), which was significantly lower than that of mucinous cystadenoma (334.2 ± 58.5 ms, mean ± SEM) or serous cystadenoma (237.0 ± 45.4 ms, mean ± SEM). There was no difference in T2* values between endometrioma and mature cystic teratoma (64.1 ± 22.6 ms, mean ± SEM). Receiver operating characteristics curve analysis revealed that optimal cut‐off value for differential diagnosis of endometrioma and mucinous or serous cystadenoma was 149.2 ms as T2* value, which has an area under the curve of 0.95 (sensitivity = 92.4%, specificity = 78.6%). Conclusion: T2* values were useful to diagnose various types of ovarian cyst/tumor. [ABSTRACT FROM AUTHOR]

Objects: There is growing evidence that sphingosine 1-phosphate (S1P) is involved in inflammatory diseases. As endometriosis is known as an inflammatory disease, we investigated the role of S1P system in the development of endometriosis. Methods: The expression of sphingosine kinase (SphK) 1 in endometriosis lesions was examined by immunohistochemistry. The cystic fluid of ovarian cysts/tumors were obtained to measure S1P concentrations. Endometriotic stromal cells (ESC) derived from endometrioma were used for in vitro experiments. Results: Sphingosine kinase 1 was detected in epithelium and stromal cells of endometriotic lesions. The mean S1P concentration in the cystic fluid of endometriomas was higher than that in nonendometriomas significantly (98.2 nM vs less than 1.5 nM, P <.01). Interleukin-1β (IL-1β) or transforming growth factor-β exhibited 2.7-fold and 11.5-fold increase in SphK1 messenger RNA (mRNA) expression in ESC, respectively (P <.01). Higher dose of S1P (125nM) increased the cell number of ESC by 20%, and low dose of S1P (1.25 nM and 12.5 nM) induced IL-6 mRNA production and IL-6 secretion by ESC dose-dependently. JTE013, an antagonist for S1PR2, partially suppressed IL-6 induction by S1P (P <.05). JTE013 and VPC23019, an antagonist for S1PR1 and S1PR3, suppressed the ESC proliferation induced by S1P. Conclusion: The present study for the first time proved that the SphK-S1P-S1PR axis play a role of accelerating inflammation and growth of endometriotic cells. [ABSTRACT FROM AUTHOR]