Sorting nexin 5 deficiency impairs MHC class II antigen presentation and inflammatory responses during tuberculosis

J Immunol. 2026 Aug 4;215(8):vkag217. doi: 10.1093/jimmun/vkag217. ABSTRACT Tuberculosis (TB) remains one of the leading causes of death from a single infectious agent worldwide, yet the host pathways that regulate antigen presentation and lung inflammation during Mycobacterium tuberculosis (Mtb) infection are incompletely defined. Sorting nexin 5 (SNX5) is a protein implicated in endosomal trafficking, antigen … Read more

Enforcing mTORC1 activity in therapeutic CD4+ T cells promotes persistence but eventual immune exhaustion

J Immunol. 2026 Aug 4;215(8):vkag206. doi: 10.1093/jimmun/vkag206. ABSTRACT There is substantial interest in developing novel engineering strategies to promote the sustained metabolic fitness of therapeutic T cells. We previously showed that overexpression of RAS homologue enriched in brain (RHEB), a positive regulator of mammalian target of rapamycin complex 1 (mTORC1), promotes aerobic glycolysis and increases … Read more

Identification of a regulatory allosteric site in Arid5a unveils a therapeutic axis for systemic inflammation

J Immunol. 2026 Aug 4;215(8):vkag215. doi: 10.1093/jimmun/vkag215. ABSTRACT Adenine-thymine (AT)-rich interactive domain-containing protein 5a (Arid5a) is an RNA-binding protein (RBP) that post-transcriptionally stabilizes mRNAs encoding proinflammatory mediators, including Interleukin-6 (IL-6), thereby amplifying inflammation. However, structural basis and regulatory mechanisms of Arid5a function remain poorly defined. In this study, we identified and characterized a conserved allosteric … Read more

Fluid shear stress as a co-stimulatory cue to enhance T cell priming and restore activation in cancer patient T cells

J Immunol. 2026 Aug 4;215(8):vkag166. doi: 10.1093/jimmun/vkag166. ABSTRACT Cancer patient-derived T cells often exhibit impaired activation and functional responsiveness due to chronic antigen exposure and therapy-induced immune dysregulation, limiting the efficacy of current immunotherapies. Mechanical forces, such as fluid shear stress (FSS), are emerging as critical regulators of immune cell activation, yet their role in … Read more

Elastase and myeloperoxidase participate in neutrophil extracellular trap release stimulated by SARS-CoV-2

J Immunol. 2026 Aug 4;215(8):vkaf313. doi: 10.1093/jimmun/vkaf313. ABSTRACT COVID-19 is a disease triggered by SARS-CoV-2 and some individuals develop a severe form that can progress to multiple organ failure. Neutrophils have been described as responsible for the release of neutrophil extracellular traps (NETs). The role of the elastase and myeloperoxidase (MPO) in NET release by … Read more

IL-17-driven transcriptional programs in muscle fibroblasts are not required for pathogenesis in murine anti-histidyl-tRNA synthetase (Jo-1) myositis

J Immunol. 2026 Aug 4;215(8):vkag225. doi: 10.1093/jimmun/vkag225. ABSTRACT Idiopathic inflammatory myopathy (IIM) is a systemic autoimmune disease targeting muscle and extramuscular organs, but the molecular mechanisms driving IIM pathogenesis remain largely undefined. Muscle fibroblasts are central to orchestrating inflammation in myositis. Here, we investigated muscle fibroblast dynamics using a single-cell RNA sequencing approach in an … Read more

CD151 identifies a cytotoxic CD4 T cell population enriched in people with HIV that later develop cancer

J Immunol. 2026 Aug 4;215(8):vkag208. doi: 10.1093/jimmun/vkag208. ABSTRACT People with HIV (PWH) exhibit persistent immune activation despite effective antiretroviral therapy, contributing to risk of non-AIDS-associated comorbidities such as cancer. Cell populations reflecting immune remodeling trajectories preceding malignancy are poorly characterized. Using peripheral blood mononuclear cells from an adult cohort (25-65 yr), we quantified the tetraspanin … Read more

Peptide exchange-competent class I MHC molecules produced in eukaryotic cells for rapid production of MHC multimers

J Immunol. 2026 Aug 4;215(8):vkag210. doi: 10.1093/jimmun/vkag210. ABSTRACT Class I MHC peptide (MHC-Ip) multimers are well-established reagents that detect antigen-specific T cells. The classical method for production of MHC-Ip multimers begins with the expression of MHC heavy chains (HCs) and β2-microglobulin (β2m) subunits as inclusion bodies in Escherichia coli and is followed by denaturant solubilization, … Read more

IL-22 synergizes with IL-17 to promote mucosal inflammation and bone loss

J Immunol. 2026 Jul 10;215(7):vkag186. doi: 10.1093/jimmun/vkag186. ABSTRACT Interleukin (IL)-22 mediates immune cell communication with nonhematopoietic cells and was shown to exert protective or destructive effects in different disease contexts. In the oral mucosal disease periodontitis, IL-22 has been associated with increased tissue destruction, although cause-and-effect evidence and the underlying mechanisms are lacking. Here, we … Read more

FcγRIII blockade prevents anti-HLA-mediated platelet clearance in a humanized murine model of platelet transfusion refractoriness

J Immunol. 2026 Jul 10;215(7):vkag195. doi: 10.1093/jimmun/vkag195. ABSTRACT Immune platelet transfusion refractoriness (iPTR) is a major complication in transfusion medicine. Although anti-HLA antibodies are recognized contributors, the mechanisms by which they drive platelet clearance remain incompletely defined. We examined sera from 18 patients with iPTR and found that anti-HLA antibodies induced uptake of human platelets … Read more

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