The Journal of Immunology

Mechanism of SGLT2 inhibitors in improving immune imbalance in diabetic mice with sepsis via regulating macrophage M2 polarization through the APOC1/HMGB1/TLR4 axis

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J Immunol. 2026 Aug 29;215(9):vkag240. doi: 10.1093/jimmun/vkag240. ABSTRACT This study aimed to investigate the mechanism by which the sodium-glucose cotransporter-2 (SGLT2) inhibitor dapagliflozin improves immune imbalance in sepsis with diabetes, focusing on its regulation of macrophage M2 polarization through the APOC1/HMGB1/TLR4 axis. A mouse model of type 2 diabetes was established through intraperitoneal injection of … Read more

The Qβ bacteriophage nanoparticle contributes to the adjuvanticity of antiglycan vaccines through a unique inflammatory pathway

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J Immunol. 2026 Aug 29;215(9):vkag252. doi: 10.1093/jimmun/vkag252. ABSTRACT Current glycoconjugate vaccines often fail to induce durable B cell memory or to provide sufficiently high-affinity antibodies limiting their utility for prophylactic protection against most bacterial and fungal pathogens. We address this limitation by engineering a chemically functionalized protein nanoparticle vaccine capable of eliciting protective nanomolar affinity … Read more

Distinct effects of two different human interferon-alpha subtypes on indicators of T-cell proliferation, activation and inhibition

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J Immunol. 2026 Aug 29;215(9):vkag259. doi: 10.1093/jimmun/vkag259. ABSTRACT Humans produce 12 distinct interferon alpha (IFN-α) subtypes that were previously thought to be functionally redundant. Recent studies have revealed that IFN-α subtypes differ in their ability to control different viral infections. However, little is known about how IFN-α subtypes differentially modulate immune cells to mediate these … Read more

A circular RNA modulates IL-6 transcription via HuR-dependent stabilization of C/EBPβ mRNA

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J Immunol. 2026 Aug 29;215(9):vkag251. doi: 10.1093/jimmun/vkag251. ABSTRACT Inflammatory responses require precise posttranscriptional control of gene expression, yet the contribution of circular RNAs (circRNAs) to this process remains poorly understood. Here, we performed circRNA sequencing in murine macrophages stimulated with lipopolysaccharide (LPS) and identified dynamic and stimulus-dependent changes in circRNA expression. Among 1,298 high-confidence circRNAs, … Read more

High-mobility group N proteins are required for regulation of antigen-presentation genes in macrophages

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J Immunol. 2026 Aug 29;215(9):vkag256. doi: 10.1093/jimmun/vkag256. ABSTRACT The expression, localization, and secretion of certain chromatin proteins are tightly regulated in response to inflammatory challenges or tissue damage. High mobility group (HMG) nucleosome-binding proteins can translocate out of the nucleus to act as alarmins in immune cell communications. The consequences of nuclear depletion of HMGs … Read more

Prostaglandin D2 production in obese mice is associated with reduced lung inflammation and improved control of Francisella tularensis and Bordetella pertussis infection

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J Immunol. 2026 Aug 29;215(9):vkag254. doi: 10.1093/jimmun/vkag254. ABSTRACT Obesity is a risk factor for severe respiratory viral infections, but its impact on bacterial respiratory diseases remains unclear and is sometimes paradoxical. Herein, we demonstrate that diet-induced obese, male C57BL/6J mice exhibited increased resistance to pulmonary infection with Francisella tularensis and Bordetella pertussis compared with lean … Read more

A gavage-fomite based method to generate mouse models with natural microbiota

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J Immunol. 2026 Aug 29;215(9):vkag242. doi: 10.1093/jimmun/vkag242. ABSTRACT Laboratory-raised specific pathogen-free (SPF) mice have been indispensable for fundamental immunology research, yet their reliability in predicting human clinical outcomes has been questionable. A major factor contributing to this disconnect is the sanitized housing environment, which deprives laboratory mice of physiological microbial exposure critical for immune maturation. … Read more

Exacerbation of inflammatory bone loss in TET2-driven clonal hematopoiesis

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J Immunol. 2026 Aug 29;215(9):vkag248. doi: 10.1093/jimmun/vkag248. ABSTRACT Clonal hematopoiesis of indeterminate potential (CHIP) arises from age-related somatic mutations in hematopoietic stem cells in the bone marrow (BM), driving clonal expansion and altered phenotypes. Loss-of-function mutations in the epigenetic regulator TET2 are among the most frequent in CHIP and increase the risk of hematologic malignancies … Read more

Immunopeptidomics-driven MHC class II peptide-binding motif discovery for 2 common canine DR alleles

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J Immunol. 2026 Aug 29;215(9):vkag243. doi: 10.1093/jimmun/vkag243. ABSTRACT Despite the central role of major histocompatibility complex (MHC) class II in adaptive immunity, peptide-binding motifs have yet to be characterized for any canine MHC class II allele. Here, we report the first immunopeptidomics-derived binding motifs for DLA-DRB1*015:01 (DLA-DR15) and DLA-DRB1*012:01 (DLA-DR12), 2 alleles overrepresented in breeds … Read more

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