Early-onset preeclampsia (EOPE) is a severe pregnancy complication associated with defective trophoblast differentiation and functions at implantation, but manifestation of its phenotypes is in late pregnancy. There is no reliable method for early prediction and treatment of EOPE. Adrenomedullin (ADM) is an abundant placental peptide in early pregnancy. Integrated single-cell sequencing and spatial transcriptomics confirm a high ADM expression in the human villous cytotrophoblast and syncytiotrophoblast. The levels of ADM in chorionic villi and serum were lower in first-trimester pregnant women who later developed EOPE than those with normotensive pregnancy. ADM stimulates differentiation of trophoblast stem cells and trophoblast organoids in vitro. In pregnant mice, placenta-specific ADM suppression led to EOPE-like phenotypes. The EOPE-like phenotypes in a mouse PE model were reduced by a placenta-specific nanoparticle-based forced expression of ADM. Our study reveals the roles of trophoblastic ADM in placental development, EOPE pathogenesis, and its potential clinical uses.

B cells constitute a diverse and adaptable immune cell population with functions that can vary according to the environment and circumstances. The involvement of B cells in pregnancy, as well as the associated molecular pathways, has yet to be investigated. This review consolidates current knowledge on B cell activities and regulation during pregnancy, with a particular focus on the roles of various B cell subsets and the effects of B cell-derived factors on pregnancy outcomes. Moreover, the review examines the significance of B cell-associated autoantibodies, cytokines, and signaling pathways in relation to pregnancy complications such as pregnancy loss, preeclampsia, and preterm birth.

The imbalance of immune response plays a crucial role in the development of diseases, including glioblastoma. It is essential to comprehend how the innate immune system detects tumors and pathogens. Endosomal and cytoplasmic sensors can identify diverse cancer cell antigens, triggering the production of type I interferon and pro-inflammatory cytokines. This, in turn, stimulates interferon stimulating genes, enhancing the presentation of cancer antigens, and promoting T cell recognition and destruction of cancer cells. While RNA and DNA sensing of tumors and pathogens typically involve different receptors and adapters, their interaction can activate adaptive immune response mechanisms. This review highlights the similarity in RNA and DNA sensing mechanisms in the innate immunity of both tumors and pathogens. The aim is to enhance the anti-tumor innate immune response, identify regions of the tumor that are not responsive to treatment, and explore new targets to improve the response to conventional tumor therapy and immunotherapy.

Neuroinflammation is a crucial driver of multiple neurodegenerative diseases, including Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS) and Parkinson’s disease (PD). Yet, therapeutic targets for neurodegenerative diseases based on neuroinflammation still warrant investigation. CD22 has been implicated in neuroinflammatory diseases, namely AD. Specifically, plasma soluble CD22 (sCD22) level is upregulated in patients with AD. Direct experimental evidence for the role of CD22 in neuroinflammation is needed, as is a better understanding of its impact on microglia activation and therapeutic potential. Here we reported that sCD22 promotes neuroinflammation both in vivo and in vitro. sCD22 activated microglia via both p38 and ERK1/2 signaling pathway for the secretion of TNFα, IL-6 and CCL3. Moreover, sCD22 activated microglia via sialic acid binding domain and 2,6 linked sialic acid glycan on sCD22. The pivotal therapeutic potential of targeting CD22 was demonstrated in Amyloid β (Aβ) induced-neuroinflammation in hCD22 transgenic mice. Suciraslimab improved working memory and resolved neuroinflammation in vivo. Further, membrane CD22 inhibited Amyloid β (Aβ) induced-NFκB signaling pathway and mechanistic study delineated that suciraslimab suppressed Aβ-induced IL-1β secretion in human microglia and PBMC. Suciraslimab also suppressed IL-12 and IL-23 secretion in human PBMC. Moreover, suciraslimab reduced the surface expression of α4 integrin on B cells. Intriguingly, we discovered that CD22 interact with Aβ and suciraslimab enhanced internalization of CD22-Aβ complex in microglia. Our data highlights the importance of sCD22 in driving neuroinflammation and the dual mechanism of targeting CD22 to resolve Aβ-induced inflammation and promote Aβ phagocytosis.

The rising global incidence of inflammatory bowel disease (IBD) is associated with menstrual cycle irregularities and reduced anti-Müllerian hormone (AMH), a key biomarker for premature ovarian insufficiency (POI), highlighting reproductive risks for women of childbearing age. Using a dextran sodium sulfate (DSS)-induced IBD mouse model, we observed decreased ovarian weight, increased follicular atresia, and disrupted estrous cycles. Ovarian transcriptomics revealed IBD-induced upregulation of aging-associated genes, with enrichment in senescence, oxidative stress response, and senescence-associated secretory phenotypes. Comparative analysis with single-cell RNA-seq data demonstrated transcriptional parallels between IBD and natural ovarian aging. Flow cytometry confirmed elevated ovarian T cells, CD8⁺ T cells, and macrophages, indicating localized inflammation, while peripheral blood mononuclear cells exhibited similar immune activation. TUNEL assays and qPCR confirmed accelerated ovarian aging, with increased granulosa cell apoptosis and upregulated senescence markers. Despite after an 89-day recovery, persistent follicular depletion, hormonal imbalance, and estrous irregularities suggested irreversible ovarian dysfunction. Our findings establish that IBD induces ovarian inflammation, depletes ovarian reserve, and accelerates aging, leading to long-term fertility impairment. This study clarifies IBD-POI mechanisms, informing potential therapeutic interventions for preserving fertility in affected women.