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During pregnancy, trophoblast cells sustain the maternal–fetal tolerance via expressing and secreting various chemokines and cytokines. Our previous study revealed the expression of interleukin-35 (IL-35) in human first-trimester trophoblasts. Here we show that IL-35 is expressed in both human first-trimester primary trophoblast cells and a trophoblast cell line. Trophoblast cells inhibit the proliferation of human naive conventional T cells (Tconv cells) and convert suppressed Tconv cells into iTR35 in an IL-35-dependent manner. Mechanistically, trophoblast cell derived IL-35 mediates its function through phosphorylation of STAT1 and STAT3. In vivo studies confirm that mice with immunologically spontaneous abortion have lower levels of IL-35 and iTR35 cells at the maternal–fetal interface, and neutralizing anti-IL-35 mAb enhances abortion rates. Meanwhile, exogenous IL-35 induces iTR35 and prevents immunological abortion. Our findings thus suggest that trophoblast cells have a critical function in preserving maternal–fetal tolerance via secreting IL-35 during pregnancy. Trophoblasts play a critical role in maintaining immunological tolerance at maternal–fetal interface. Here the authors show that IL-35 is made by trophoblasts, converts T cells to immune tolerant iTR35 cells, and is critical to prevent spontaneous abortion. [ABSTRACT FROM AUTHOR]

Background: Small cell lung cancer (SCLC) has a strong invasive ability and a high degree of malignancy, so accurate prognosis prediction is crucial for making the most favorable treatment decision.Unfortunately, there is a scarcity of prognostic indicators specific to SCLC. Reticulocyte levels in blood parameters have been linked to the prognosis of various malignancies. Given SCLC's aggressive characteristics, identifying reliable prognostic markers, such as reticulocyte counts, becomes pivotal in enhancing prognostic accuracy and guiding effective therapeutic strategies., Objective: This study aimed to evaluate the predictive power of the immature reticulocyte fraction (IRF) to mature reticulocyte fraction (MRF) ratio (IMR) for survival outcomes in patients with SCLC., Materials and Methods: A retrospective analysis was conducted on 192 patients with small cell lung cancer (SCLC). The median values of various prognostic indicators, such as IMR, IRF, MRF, reticulocyte count (RET), SII (systemic immune-inflammatory index), were utilized as cutoff points, categorizing patients into high and low groups. The Kaplan-Meier method, univariate, multivariate analyses Cox regression, and C-index were used to analyze the prognostic factors for overall survival (OS)., Results: In our cohort, 138 (71.9 %) were male, 119 (62 %) were smokers, and 82 (57.3 %) were older than 60 years old. The median survival time was 18.15 months.Higher mortality was observed in the high IMR and high IRF groups, while the high MRF group exhibited lower mortality. At the same time, mortality was lower in the high MRF group. Univariate analysis showed that smoking history ( P  = 0.006), tumor stage ( P  = 0.002), chemotherapy cycle ( P  = 0.014), IMR ( P  = 0.01), and many other factors significantly affected the prognosis of SCLC. Multivariate analysis demonstrated that elevated IMR was an independent adverse predictor of OS ( P  = 0.039, HR = 0.330). Spearman test confirmed that the prognostic indicators IRF, IMR, and SII were positively correlated with the overall survival rate of patients with SCLC. Kaplan-Meier analysis showed that the OS rate of patients with high IMR was significantly worse ( P  = 0.0096). In addition, we found that IMR was superior to IRF in distinguishing patients with different outcomes in the low and high groups ( P  < 0.05). Our novel integration index, combining IMR with the TNM stage system and SII index, exhibited superior prognostic value compared to the original index. Additionally, the combination of prognostic indicators IMR and SII significantly stratified stage I-II SCLC patients ( P ＜0.05)., Conclusions: The prognostic index based on peripheral blood IMR stands out as an independent predictor for SCLC patients pre-treatment. Its accessibility through routine blood analysis facilitates immediate clinical application without requiring prolonged scientific research validation. The integration of IMR with the TNM score enhances survival prediction and risk stratification. Notably, when combined with the SII score, the new IMR index demonstrates significant improvements in prognostication for stage I-II small cell lung cancer., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors. Published by Elsevier Ltd.)

Regulatory B cells (Breg cells) play critical roles in modulating immune responses during autoimmune diseases and infection. Here we explored the participation of two main Breg subsets, including IL-10 + Breg (B10) and IL-35 + Breg cells, in maintaining successful pregnancy. We first observed an elevated percentage of B10 cells in peripheral blood from first-trimester pregnant women compared with non-pregnant controls. Serum from pregnancy induced the augmentation of B10  in peripheral blood mononuclear cells from non-pregnant women. In animal models, we demonstrated that there were significant augmentation of B10 cells and obvious increase of IL-10 level in splenic B cells from normal pregnant mice compared to that in abortion-prone pregnant mice and virgin mice. Further analysis showed that both hCG and IL-35 suppressed the proliferation of mouse splenic B cells. Moreover, IL-35 induced the expansion of both mouse splenic B10 and IL-35 + Breg cells while hCG only mediated the generation of B10 cells. Subsequent study in mice demonstrated that the activation of STAT1 and STAT3 in B cells caused by IL-35 and the activation of STAT3 caused by hCG were the predominant mechanism of IL-35 + Breg and B10 cells augmentation. These findings suggested that hCG and IL-35 induced the amplification of B10 and IL-35 + Breg cells which played a vital peripheral regulatory role during pregnancy., (Copyright © 2019 Elsevier Inc. All rights reserved.)