Immunoglobulin G (IgG) is one of the main contributors to inflammation due to its function and amount in circulation. This function of IgG can swing from pro- to anti-inflammatory states with small changes in glycan structure at Asparagine-297 of IgG Fc domain. This variation is implicated in pathophysiology of autoimmune diseases such as rheumatoid arthritis. Although our understanding about the structure-function relation of IgG Fc glycosylation has immensely increased for the last four decades, it is still limited about the regulators of this glycan structure. To broaden our understanding, ex-vivo cell cultures derived from lymph node (LN), spleen (SP) and bone marrow (BM) of K/BxN mouse, which is a model for autoantibody-dependent rheumatoid arthritis, were established. The glycan structures of antigen purified anti-glucose-6-phosphate isomerase (anti-GPI) autoantibody heavy chains produced in these cultures were characterized using HPLC. According to the results, while IgG produced in LN is decorated with the highest amount of pro-inflammatory agalactosylated structure, IgG produced in SP has the highest amount of anti-inflammatory sialylated structure. Interestingly, IgG produced in BM stands in between them due to more balanced distribution of glycan structures. In conclusion, the ex-vivo cell cultures of LN, SP and BM were successfully established, and the contribution of IgG to on-going inflammation is regulated by the production site of anti-GPI autoantibody via glycan structures. In addition, N-glycan profile of anti-GPI autoantibody produced in LN closely replicates the N-glycan profile for anti-GPI autoantibody from K/BxN serum indicating that anti-GPI autoantibody in circulation is heavily produced in LN.

Emerging evidence indicates that macrophages play important roles in hematopoiesis in addition to their immune functions. The well-known immune-unrelated functions of macrophages include their roles in hematopoiesis, especially quality control of hematopoietic stem/progenitor cells (HSCs/HSPCs), supporting erythropoiesis, and megakaryopoiesis. Several studies, most using mouse models, have explored the roles of macrophages in hematopoiesis in different organs such as the yolk sac (YS), fetal liver (FL), bone marrow (BM) and spleen (SP). We have recently documented the potential roles and underlying mechanisms of macrophages in myeloproliferative neoplasm (MPN), aplastic anemia (AA), and idiopathic thrombocytopenic purpura (ITP). In this article, we review origin of macrophages, introduce the roles of macrophages in HSCs/HSPCs, erythropoiesis, and megakaryopoiesis in four hematopoietic organs, summarize the recent advances of macrophages in MPN, AA and ITP. Finally, we outline the unresolved questions that future studies should address to explore in greater depth of macrophages' role in both normal and disordered hematopoiesis.

ObjectiveThis study aims to investigate the association between gut microbiota dysbiosis and phenotypic alterations in immune cells across multiple tissues in a collagen-induced arthritis (CIA) mouse model, and to elucidate the bidirectional regulatory mechanisms underlying the interaction between the gut microbiota and host immune responses.MethodsTwelve 6-8-week-old male DBA/1 mice were randomly assigned to either a collagen-induced arthritis (CIA) model group (n=6) or a normal (NOR) group (n=6). At the end of the experiment, feces, peripheral blood (PB), spleen (SP), intestinal segments, joint tissues and serum were collected. We employed an integrated analytical approach comprising fecal 16S ribosomal DNA gene sequencing, short-chain fatty acid (SCFA) metabolomics, flow cytometric detection of IgA-coated bacteria, immune phenotyping by flow cytometry, and cross-group network analysis to systematically evaluate gut microbial composition and host cellular immune profiles.ResultsCIA mice developed polyarthritis, accompanied by a decrease in splenic T and NK cells and an increase in B cells. CD8+ T cells were significantly increased in mesenteric lymph nodes (MLN) and intestinal mucosa (IM). The gut microbiota exhibited reduced α-diversity, enriched Bacteroidetes, depleted Firmicutes, and decreased Lachnospiraceae_NK4A136_group. Fecal SCFA levels declined, while the proportion of IgA-coated bacteria increased. Functional prediction analysis indicated downregulation of microbial gene pathways associated with xylan decomposition, amino acid metabolism, and drug efflux, whereas pathways related to cell wall synthesis were upregulated. Cross-omics analysis confirmed significant correlations between these immune cells and specific bacterial genera.ConclusionThe reduction of SCFAs synthesis caused by gut microbiota dysregulation in CIA mice is related to the expansion of intestinal CD8+ T cells and may further promote the imbalance of T/B cells in the spleen; this gut microbiota -SCFA- CD8+ T cell axis may be involved in the occurrence and development of arthritis.

Tissue specific requirement for the inv(16) oncogene CBFB::MYH11 implies unique leukemia survival mechanisms in the bone marrow microenvironment

Targeting a novel surface antigen, ryk, with the antibody-drug conjugate, slv-404, is effective in richter transformation patient-derived xenografts

Optimizing establishment of high need pediatric Acute Myeloid Leukemia (AML) patient derived xenograft (PDX) models

Abstract Description Adjuvants enhance the magnitude and durability of antibody-mediated immunity to vaccines, even with lower doses of antigen. However, limited studies have directly compared how different adjuvants might influence immune responses elicited under such dose-sparing regimens. Here, we investigate three different adjuvants in mice—AddaVax (MF59-like), IMDQ-PC (TLR7/8 agonist), and IMDQ-PC complimented with SDI (RIG-I agonist)—for their capacity to promote effective antibody-mediated immunity when combined with a dose-sparing quantity of quadrivalent inactivated influenza vaccine (QIV). We found that each adjuvant displayed a unique immune response skewing that correlated with protection during infection. AddaVax displayed a Th2 biased response in contrast to IMDQ-PC and IMDQ-PC+SDI’s observed Th1 bias. All three adjuvants induced substantial germinal center B cell (GCBC) responses in the draining lymph nodes (dLNs), however only IMDQ-PC vaccines displayed significant immune response in the spleen (SP). Consistent with GCBC kinetics, CD4+ follicular helper T cells were also highly expanded in adjuvant immunized mice. IMDQ-PC vaccines also appeared to more favorably promote extrafollicular B cell response with markedly increased numbers of early plasmablasts and an activated memory precursors population in both the dLNs and SPs. Similarly, IMDQ-PC vaccines showed a significant increase in swIg CD80+ PD-L2+ memory B cells which are thought to be primarily GC-derived. Funding Sources Supported by T32AI007647 awarded to M.J.P.; NIH/NIAID R21AI151229; R21AI176069; R44AI176894; CEIRR contract number 75N93021C00014; and by NIAID SEM-CIVIC contract number 75N93019C00051. Topic Categories Vaccines and Immunotherapy (VAC)

Triploid cyprinid fish (TCF, 3N = 150) is a novel hybrid fish showing great disease resistance during aquaculture processes. However, the majority of Aeromonas strains act as opportunistic pathogens that can cause a variety of diseases and pose a notable health risk. In this investigation, a novel Aeromonas sp. AS1-4 was retrieved from the spleen (SPL) of moribund cyprinid fish. Whole genome sequencing (WGS) was employed to characterize its virulence features and signal regulation. Thereafter, TCFs were infected with strain AS1-4 for pathological analysis. Strain AS1-4 challenge could cause abnormal glycogen deposition in the liver (LIV) of TCFs, accompanied by significant alteration of physiological response. Furthermore, expression patterns of pivotal immune-related genes were markedly elevated in TCFs post-infection. Transcriptomic analysis revealed that strain AS1-4 infection may exert a profound impact on insulin signaling pathway and steroid biosynthesis. These results may contribute to the comprehension of molecular characteristics in fish infected with Aeromonas sp. AS1-4.

Background:Benign prostatic hyperplasia (BPH) affects >50% of males aged ≥50 years, causing lower urinary tract symptoms that significantly impair quality of life. While acupuncture is increasingly used for BPH management, its acupoint selection patterns remain unstandardized.Methods:Clinical studies on acupuncture/moxibustion for BPH published before September 30, 2024, were retrieved from CNKI, WANFANG, VIP, PubMed, and ScienceDirect. Acupoint patterns were analyzed using the Traditional Chinese Medicine Inheritance Assistance Platform (TCMISS).Results:Among 270 articles, 85 met the inclusion criteria. Sixty-one acupoints were identified, with high-frequency selections including Guanyuan (CV4), Zhongji (CV3), Sanyinjiao (SP6), Qihai (CV6), Shenshu (BL23), Shuidao (ST28), Pangguangshu (BL28), Yinlingquan (SP9), Qugu (CV2), and Ciliao (BL32). The Conception Vessel (CV), Bladder (BL), and Spleen (SP) meridians were predominantly used, primarily distributed in the chest/abdomen (EX-CA) and back/waist (EX-BW) regions. Association rule analysis revealed strong correlations among acupoints, with key combinations being Zhongji (CV3)-Sanyinjiao (SP6), Guanyuan (CV4)-Qihai (CV6), and Guanyuan (CV4)-Sanyinjiao (SP6). Core therapeutic clusters centered on Zhongji (CV3), Guanyuan (CV4), and Shenshu (BL23), integrated with Sanyinjiao (SP6), Shuidao (ST28), and Yinlingquan (SP9).Conclusions:Acupuncture for BPH primarily targets CV4, CV3, SP6, CV6, BL23, ST28, BL28, SP9, CV2, and BL32, reflecting their strong therapeutic relevance. These findings highlight meridians and acupoints potentially critical for symptom alleviation. However, rigorous clinical trials are warranted to validate efficacy and optimize protocols. This review provides a foundation for advancing evidence-based acupuncture interventions in BPH management.

The majority of immune cells in the human body exist within the tissues rather than in the circulation. Nevertheless, most of our knowledge of the human immune system is biased towards the characterization and understanding of circulating immune cell populations because the latter are readily sampled, whereas cells in tissues are difficult to obtain and/or are limited to single sites of disease. Tissue-resident cells differ from circulating cells due to tissue-specific niche adaptations that influence their phenotype and function. For instance, T cells in tissues, resident memory (TRM cells), exhibit tissue-specific properties that allow optimal protection from infection due to an acquired ability to coordinate rapid and efficacious pathogen clearance. Thus, to fully understand T-cell responses in various pathological conditions one must focus on the properties of TRM cells and how they have been shaped by their environment. Moreover, one must sample and analyze T cells from multiple tissues, optimally from the same individual, to determine how infectious, cancer, or autoimmune challenge is affecting homeostatic function. Our longstanding collaboration with the organ procurement organization, LiveOnNY, provides unique access to multiple lymphoid, mucosal, and peripheral tissues from organ donors where consent for research use has been obtained. These samples have enabled characterization of human tissue resident memory T cells and other immune cell types across a variety of tissues. Concomitant with this endeavor, we developed and refined a series of methodologies critical for extracting immune cells from tissue for the purpose of phenotypic and mechanistic interrogation. Here, we describe our optimized protocols for processing select human tissues and the requisite coordination and considerations for their maximal yield and tissue quality. © 2025 Wiley Periodicals LLC. Basic Protocol 1: Isolation of immune cells from blood-rich sites [spleen (SPL), blood (BLD), bone marrow (BOM)] Basic Protocol 2: Isolation of immune cells from lymph nodes, tonsils, and thymus [iliac lymph nodes (ILN), lung lymph nodes (LLN), mesenteric lymph nodes (MLN), colonic lymph nodes (CLN), hepatic lymph nodes (HLN), tonsils (TON), thymus (THY)] Basic Protocol 3: Isolation of immune cells from the lungs [lung (LNG), bronchioalveolar lavage (BAL)] Basic Protocol 4: Isolation of immune cells from the intestines [jejunum epithelial layer (JEL), jejunum lamina propria (JLP), colon epithelial layer (CEL), colon lamina propria (CLP)] Basic Protocol 5: Isolation of immune cells from the liver (LVR) Basic Protocol 6: Immune cell staining for flow cytometry.

Optimizing Establishment of High Need Pediatric Acute Myeloid Leukemia Patient Derived Xenograft Models

MyD88L265P Mutation Impairs Bone Marrow Hematopoietic Stem Cell Function in a Cell-Autonomous Way Resulting in an MPN-like Phenotype

Investigating the Role of SWI/SNF Chromatin Remodeling Component, ARID2, in Normal and Malignant B Cells

TET2 Deficiency Cooperates with MSH6 Mutation to Promote the Progression of MDS/MPN through Increasing Tumor Stem Cell Frequency

The role of bile acid in regulating head-kidney, spleen and skin immune function of on-growing grass carp (Ctenopharyngodon idella)

The paper deals with ethnomedicinal information on 54 plant species (belonging to 33 families) collected from field survey amongst three tribes viz., Gond, Korku and Gaiki of Betul district, Madhya Pradesh. An analysis of data has indicated that eight plant species are employed as antidote to snake bite and scorpion sting, six to treat fever. five for rheumatism, four to treat cold, cough, skin diseases, as anthelmintic and tonic, and three for stomach diseases while two species to treat impotency, cuts, wounds and as diuretic. On the other hand, only single species has been referred for a number of other ailments like eye diseases, spermatorrhoea, spleen enlargement, tuberculosis, mouth sore, boil, asthma, liver disorder, toothache, bone fracture, abortifacient, antifertility, and in veterinary. Further, a comparison with the concerned literature has revealed that 23 ethnomedicinal uses of plants have not been reported earlier.

CXCL13/CXCR5 axis mediates IgM+ B cell migration through AKT and STAT3 signaling pathways in Nile tilapia (Oreochromis niloticus)

Abstract Introduction: Acute myeloid leukemia (AML) is the most common acute type of leukemia in adults characterized by chromosomal abnormalities and gene mutations. While inhibitors have shown promise targeting FLT3 mutations, resistance to these inhibitors can emerge. Similarly, inhibitors targeting IDH1 and IDH2 mutations showed promise, yet the emergence of drug resistance poses a significant challenge. In this study, a panel of AML PDX models with multiple gene alterations was established to support the development of new therapies. Methods: The systemic AML PDX models were established using patients’ peripheral blood (PB) or bone morrow (BM) injected intravenously and expanded in vivo by using splenic tumor cells. One AML PDX model derived from patient skin was established subcutaneously. Expression of human CD45+ in PB cells for systemic models or tumor volume for the subcutaneous model was used to monitor the tumor burden. Leukemic loads (hCD45+ cells) were measured in PB, spleen (SP), and BM. Tumors were categorized following tumor immunophenotyping, histology, and RNA sequencing/Whole Exome Sequencing. For in vivo efficacy studies, animals were grouped 3-5 weeks after systemic tumor cells inoculation and treated with AC220 (1, 2 or 10 mg/kg, p.o., QD), Cytarabine (Ara-c, 2mg/kg, i.p., QD), 5-azacytidine (2mg/kg, i.p., QD), Sorafenib (10mg/kg, i.p., QD) and Gilteritinib (10 or 30mg/kg, p.o., QD). Results: Nine systemic and one subcutaneous AML PDX models carrying hotspot mutations (e.i. FLT3-ITD or TKD, IDH1-R132H and IDH2-R140Q) were established, showing comparable features to the clinic. Systemic AM8231 PDX model harboring FLT3-ITD mutation treated with AC220, a type II FLT3i, showed significant tumor burden reduction in PB at different time points and in SP and BM at termination, as well as a survival increase. Similarly in systemic model AM7577 with FLT3-ITD mutation treated with AC220, significant tumor burden reduction in PB was observed. Whereas using systemic model AM9626 (model with Sorafenib pretreatment history) with coexisting-FLT3-ITD/D835H TKD mutation, no significant efficacy was observed with AC220i, suggesting a FLT3-TKD mediated resistance mechanism. To overcome the resistance, Gilteritinib, a type I FLT3i, was tested in AM9626 and showed significant reduction of hCD45+ cells in PB compared to the control group, even at a lowest dose. As model AM9626 PDX also carries IDH1 mutation, the level of serum 2-HG correlated with the tumor burden. The functional effect of IDH1 inhibitor on the tumor inhibition and 2-HG level is under investigation. Conclusion: The results presented in this study showed the establishment of a panel of AML PDX models, including different subtypes and genomic features reflecting the clinic. Those models will support the preclinical evaluation of new treatments or combination modalities as well as a better understanding of drug resistance mechanisms. Citation Format: Qingzhi Liu, Jinxi Wang, Jinping Liu, Likun Zhang, Ludovic Bourre, Jingjing Wang. Characterization of acute myeloid leukemia PDX models with hotspot gene mutations for therapeutic evaluation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2827.

An emerging role of guanidine acetic acid in rescuing immune function injured by Aeromonas hydrophila in grass carp (Ctenopharyngodon idella)

Liver-X receptors (LXRs) are essential nuclear hormone receptors involved in cholesterol and lipid metabolism. They are also believed to regulate inflammation and physiological and pathological bone turnover. We have previously shown that infection with the periodontal pathogen Porphyromonas gingivalis (Pg) in mice increases the abundance of CD11b+c-fms+Ly6Chi cells in bone marrow (BM), spleen (SPL), and peripheral blood. These cells also demonstrated enhanced osteoclastogenic activity and a distinctive gene profile following Pg infection. Here, we investigated the role of LXRs in regulating these osteoclast precursors (OCPs) and periodontal bone loss. We found that Pg infection downregulates the gene expression of LXRs, as well as ApoE, a transcription target of LXRs, in CD11b+c-fms+Ly6Chi OCPs. Activation of LXRs by treatment with GW3965, a selective LXR agonist, significantly decreased Pg-induced accumulation of CD11b+c-fms+Ly6Chi population in BM and SPL. GW3965 treatment also significantly suppressed the osteoclastogenic potential of these OCPs induced by Pg infection. Furthermore, the activation of LXRs reduces the abundance of OCPs systemically in BM and locally in the periodontium, as well as mitigates gingival c-fms expression and periodontal bone loss in a ligature-induced periodontitis model. These data implicate a novel role of LXRs in regulating OCP abundance and osteoclastogenic potential in inflammatory bone loss.