Frontiers in Immunology最新文献

Kidney transplantation remains the treatment of choice for patients with end-stage renal disease, yet its long-term success continues to face major challenges, including organ shortage, rejection, and drug toxicity. With the advancement of genetic testing technologies, transplant management is progressively shifting from empirical practice toward precision medicine. This review systematically outlines four core applications of genetic testing in kidney transplantation: from pre-transplant precision donor-recipient matching and risk stratification, to peri-operative pharmacogenomics-guided immunosuppression, and finally post-transplant noninvasive rejection monitoring and infection management. By integrating high-resolution HLA typing, epitope mismatch analysis, donor-derived cell-free DNA monitoring, urinary biomarker detection, genotyping of drug-metabolizing genes such as CYP3A5, and assessment of host susceptibility variants, genetic technologies have significantly improved transplant outcomes. Despite persistent challenges in standardization, clinical translation, and ethical considerations, emerging innovations including microfluidics, nanopore sequencing, and organoid modeling are expected to further accelerate the transition of kidney transplantation into a new era of comprehensive precision management.

[This corrects the article DOI: 10.3389/fimmu.2025.1718092.].

Vascular calcification (VC) is an actively regulated pathological process that significantly increases the risk of cardiovascular events. As key cells of the innate immune system, macrophages play a dual role in VC through polarization into different phenotypes: Pro-inflammatory macrophages promote calcification by secreting pro-inflammatory factors, releasing apoptotic bodies, and producing extracellular vesicles (EVs); conversely, Anti-inflammatory macrophages inhibit calcification through anti-inflammatory factors, exosomes, plaque stabilization, and ATP/pyrophosphate (PPi) metabolism. However, under metabolic diseases such as diabetes, anti-inflammatory macrophages may exhibit pro-calcific properties. This review systematically summarizes the mechanisms of macrophage polarization in VC, discusses the application of macrophage-related biomarkers and imaging techniques in diagnosis, and highlights therapeutic strategies targeting macrophage polarization, recruitment, and activation. Finally, current challenges in dynamically monitoring macrophage polarization and context-dependent functional heterogeneity are outlined, and future research directions focusing on immunomodulation-based multi-target drug design and engineered cell therapies are proposed.

Introduction: Probiotics have emerged as a promising and safe alternative therapy for atopic dermatitis (AD) by regulating the gut microbiota-immune axis, correcting type 1/type 2 imbalance, and repairing the skin barrier.

Methods: A mouse model of AD was established using diphenylnitromethane (DNFB). Low, medium, and high doses of human milk-derived Lacticaseibacillus rhamnosus HM126 were administered to investigate its effects on the model. We observed the scratching frequency and skin lesion scores after 28 days of continuous oral administration. Serum biochemical indicators and inflammatory cytokines were measured using ELISA, whereas the gut microbiota in feces was analyzed using 16S rDNA sequencing. Non-targeted metabolomics was used to assess the changes in fecal metabolites.

Results and discussion: Compared to the DNFB group, high-dose L. rhamnosus HM126 significantly reduced scratching frequency in AD mice. The low-dose group showed significantly reduced IgE levels. Additionally, the IFN-γ/IL-4 ratio significantly increased, indicating that L. rhamnosus HM126 modulates type 1/type 2 immune factors toward equilibrium. 16S rDNA analysis revealed that L. rhamnosus HM126 significantly reduced the ACE index and Chao 1 index of the gut microbiota in mice with AD, thereby reshaping the composition of the gut microbiome. Metabolomics analysis suggested that L. rhamnosus HM126 may improve AD by influencing the levels of asiatic acid, phytosphingosine, Ser-Glu, prostaglandin F2 alpha ethylamide (PGF(2α)EA), argininosuccinic acid, L-rhamnose, and gamma-L-glutamyl-L-glutamic acid. This study demonstrated that L. rhamnosus HM126 maintains the type 1/type 2 balance and effectively modifies the gut microbiota structure and metabolic changes to improve AD. Our findings provide a scientific basis for the development of probiotic therapeutics to prevent and treat this condition.

Introduction: Cattle produce a unique antibody repertoire characterized by an exceptionally wide range of complementarity determining region 3 heavy chain (CDR3H) lengths, spanning from 1 bp to 204 bp-a feature that is extremely rare among mammals. The diversity characteristics of CDR3 segments of varying lengths and the underlying genetic and structural mechanisms remain an active area of research.

Methods: We constructed CDR3 expression libraries from splenic tissues of eight adult cattle using RACE-PCR, followed by high-throughput sequencing. CDR3 regions were analyzed statistically in accordance with IMGT standards and structural characteristics of immunoglobulins.

Results: High-throughput sequencing yielded a total of 473,067 high-quality reads. The CDR3 regions exhibited a broad length distribution, with the maximum reaching 234 bp. Based on density stacking analysis, CDR3 lengths were classified into four distinct groups: short (1~30 bp; 11.91%~16.93%), normal (31~100 bp; 81.51%~85.02%), long (101~150 bp; 0.12%~0.30%), and ultra-long (>150 bp; 0.16%~2.76%). Based on IMGT standards analysis, non-templated (N) nucleotides is the primary factor influencing CDR3 length. Each group displayed distinct preferences in V and D gene segment usage. The short CDR3 group was dominated by V1-14 and V1-39, the normal group was characterized predominantly by V1-39, while the long and ultra-long groups showed a strong preference for V1-7. Cattle possess two IgM subtypes, IgM1 and IgM2. The CDR3 length of the IgM1 subtype is primarily distributed in the short and normal groups. Within the normal CDR3 group, IgM1 exhibits a strong preference and exceptionally high utilization (70~80%) for the D4-1 gene segment. This stands in stark contrast to the usage of other D gene segments, particularly D8-2, which participates in CDR3 formation at a much lower frequency of merely 5~20%.

Discussion: In summary, our findings suggest that the diversification of bovine CDR3H length is a multifactorial process. It results not only from biased V(D)J recombination but is also influenced by the balance between exonuclease and TdT activities, specialized subregions within germline gene segments, N/P nucleotide insertions, stochastic trimming of gene ends, and the formation of unique structural motifs such as disulfide bonds. These findings provide a foundational model for understanding the architecture and generation of complex antibody repertoires.

[This corrects the article DOI: 10.3389/fimmu.2023.1115504.].

Introduction: Instant blood-mediated inflammatory reaction (IBMIR) is a major obstacle in clinical islet transplantation, leading to islet apoptosis and dysfunction due to inflammatory reaction. Xuebijing (XBJ), a traditional Chinese medicine, has been extensively used in the treatment of systemic inflammatory conditions and achieved remarkable effect. Giving these properties, XBJ holds promise in improving the outcomes of intrahepatic islet transplantation through inhibiting IBMIR.

Methods: The xenogeneic islet transplantation model was employed to evaluate the inhibitory effects of XBJ on IBMIR, while the syngeneic transplantation model was used to confirm that XBJ improves the long-term outcomes of intrahepatic islet transplantation through IBMIR suppression. In addition, studies were conducted under inflammatory conditions to demonstrate the protective effects of XBJ on islets in vitro, specifically its ability to preserve islet viability and function in an inflammatory environment.

Results: In vivo IBMIR model, XBJ significantly inhibited leukocyte infiltration, leading to reduced islet damage. In vitro, XBJ provided direct protection to islets in inflammatory stimulation, preventing apoptosis and preserving islet function. These protective effects were further demonstrated in the syngeneic islet transplantation model, where XBJ markedly improved the outcomes of intrahepatic islet transplantation.

Discussion: This study provides the evidence that XBJ improves islet transplantation outcomes through dual mechanisms targeting the IBMIR. As an already approved drug, XBJ presents a promising and readily translatable adjunctive therapy for clinical intrahepatic islet transplantation.

Introduction: Gaining insights into the molecular features associated with T cell exhaustion (TEX) can offer fresh perspectives on predicting treatment responses, and we aim to investigate TEX-related tumor associated macrophages (TAM) subset to deeply understand underlying mechanisms of immune exhaustion.

Methods: We performed pan-cancer single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics RNA sequencing (stRNA-seq) analyses to investigate the subtype of TEX-associated TAMs, exploring its spatial distribution characteristics in context of immunotherapy. The pan-cancer scRNA-seq and RNA-seq datasets were incorporated to develop the STMN2+ Macrophage Signature (STMN2.SIG), which predicts immunotherapy response based on integrative machine learning techniques. Comprehensive scRNA-seq analysis, with in vitro experiments, investigated the mechanisms by which STMN2+ TAMs influence tumor progression and immune exhaustion.

Results: A macrophage subset, STMN2+ TAMs, and an epithelial subtype, S phase Sympathoblasts were identified as TEX-related cellular subpopulations. A higher proportion of STMN2+ TAMs was observed in non-responders compared to responders in pan-cancer immunotherapy landscape. Pan-cancer STMN2.SIG performed well in predicting immunotherapy response in pan-cancer cohorts, potentially linked to intercellular interactions between STMN2+ TAMs and CD8+ Tex cells. stRNA-seq analysis confirmed that interactions and cellular distances between STMN2+ TAMs and CD8+ Tex cells impact therapy efficacy. In a co-culture system, silencing BCAP31 on TAMs drives CD8+ T cells toward an effector state in NB. And BCAP31 on TAMs is associated with modulation of JAK2-STAT3 pathway in tumor cells.

Conclusion: Our study provides pan-cancer STMN2.SIG as an outperforming approach for patient selection of immunotherapy, and advances our understanding of TAM biology and suggests potential therapeutic strategies for downregulation of BCAP31 in TAMs.

Background: The highly polymorphic Human Leukocyte Antigen (HLA) system is critical for adaptive immunity and determines compatibility in transfusion and transplantation medicine. Admixed Latin American populations, such as Colombia's trihybrid population, possess unique HLA diversity that remains poorly characterized at high resolution.

Methods: We performed high-resolution HLA typing on 11,576 Colombian blood donors from two distinct regions: the Andean and Caribbean. We analyzed allele and haplotype frequencies, Hardy-Weinberg equilibrium, linkage disequilibrium (LD), and compared genetic distances with global populations via PCA and UPGMA clustering.

Results: We identified 565 alleles and 17,317 unique haplotypes, revealing extreme diversity. A few alleles dominated each locus, yet the top 20 haplotypes had a cumulative carrier frequency of only 3.17%, highlighting a fragmented haplotype landscape. Strong LD was observed between class I and II loci (HLA-A~DQB1), indicating conserved extended haplotypes. Genetically, the Colombian cohorts formed a tight cluster, showing closest affinity to Indigenous Chilean populations, suggesting a shared Andean background.

Discussion: This study provides the first large-scale, high-resolution HLA map of Colombia, capturing the extensive immunogenetic diversity of an admixed Latin American population. Our findings are vital for improving transplant matching, understanding population-specific disease risks, and advancing equitable genomic medicine in the region.