Journal of immunology最新文献

{"title":"Context-dependent regulation of cytotoxic T lymphocytes by nuclear receptors.","authors":"Chang H Kim","doi":"10.1093/jimmun/vkag261","DOIUrl":"https://doi.org/10.1093/jimmun/vkag261","url":null,"abstract":"<p><p>Cytotoxic CD8⁺ T lymphocytes eliminate pathogen-infected and malignant cells through migration to affected tissues, cytokine production, and cytotoxic activity. A mounting body of evidence indicates that CD8 T cell differentiation into functionally different subsets, such as effector, memory, tissue-resident memory, and exhausted T cells, is controlled by a group of nuclear receptors (NRs). NRs sense signals from various physiological and environmental cues, such as nutritional, endocrine, stress/circadian, and metabolic signals, and translate them into gene-regulatory decisions. NRs act through direct and indirect DNA binding, corepressor-coactivator exchange, and transrepression of effector-associated transcription factors, thereby reshaping chromatin accessibility and metabolic programs during CD8 T cell differentiation. This review highlights major CD8 T cell-regulating pathways involving vitamin A-sensing RAR-α, sterol-responsive LXR-β and ROR-α, orphan NR4A proteins; vitamin D receptor (VDR), glucocorticoid receptor (GR), and androgen receptor (AR). Understanding the shared and separable functions of NRs and their ligands provides insights into therapeutic strategies, such as pharmacologic modulation, checkpoint blockade, and chimeric antigen receptor T cell therapies, to promote durable antitumor and antiviral CD8 T cell activities.</p>","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":"215 10","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13630429/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149110564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Programmed cell death protein 1 (PD-1) regulates metabolic activity of regulatory T cells in ischemia-induced acute kidney injury.","authors":"Oliver B Pelletier, Murat Dogan, Christopher O'Neill, Vikram Sabapathy, Didier Portilla, Rahul Sharma","doi":"10.1093/jimmun/vkag234","DOIUrl":"https://doi.org/10.1093/jimmun/vkag234","url":null,"abstract":"<p><p>Immune checkpoint inhibitor (ICPI) therapy, targeting Programmed cell death protein 1 (PD-1) and its ligands PD-L1 and PD-L2, have revolutionized cancer care. However, ICPI is linked to immune-related adverse events, including nephropathy manifesting as acute kidney injury (AKI), a rapid decline in kidney function, often progressing to renal failure. Regulatory T cells (Tregs) could mitigate AKI, caused by ischemia-reperfusion injury (IRI). Treg stability and function rely on cellular metabolism, with a distinct preference for oxidative phosphorylation (OXPHOS) over glycolysis. Although PD-1 is known to regulate metabolism of CD8 T cells, its role in controlling OXPHOS in Tregs remains underexplored. We demonstrate that PD-1 knockout (KO) mice have worse renal function after IRI when compared to wild-type mice. PD-1-deficient Tregs lose their protective ability against AKI despite retaining in vitro suppressive activity and Foxp3 expression. Transcriptomic analysis reveals altered expression of genes linked to function, proliferation, and mitochondrial metabolism in PD-1 KO Tregs as compared to wild-type Tregs. PD-1 KO Tregs exhibit reduced mitochondrial mass, membrane potential, biogenesis, and dynamics, leading to impaired mitochondrial fitness and trends for reduced expression of fatty acid transporters CD36 and Cpt1a and Glut1. Loss of PD-1 expression or antibody-mediated blockade of PD-1 attenuated OXPHOS and expression of genes related to mitochondrial metabolism in Tregs. These metabolic defects may stem from morphological alterations in mitochondria, highlighting the critical role of PD-1 in Treg-mediated nephroprotection. Our findings reveal the metabolic vulnerability of PD-1-deficient Tregs and underscore the importance of PD-1 in Treg-mediated protection against AKI with implications for ICPI-related nephropathy.</p>","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":"215 10","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149127439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-term Nlrp3 gain-of-function mutation promotes cardiac dysfunction independent of inflammasome in mice.","authors":"Mie Kurata, Kayo Takahashi, Naoe Kaneko, Kenji Kameda, Takanori Nakamura, Sho Hosokawa, Kasumi Murakami, Hideki Ogura, Satoshi Ishido, Osamu Yamaguchi, Junya Masumoto","doi":"10.1093/jimmun/vkag257","DOIUrl":"https://doi.org/10.1093/jimmun/vkag257","url":null,"abstract":"<p><p>Cryopyrin-associated periodic syndrome (CAPS) is an autoinflammatory disease caused by gain-of-function mutations in human nucleotide-binding domain, leucine-rich repeat-containing protein 3 (NLRP3), which lead to constitutive inflammasome activation and excessive IL-1β secretion. Long-term IL-1 blockade has markedly improved patient outcomes by preventing systemic inflammation and amyloidosis. However, whether chronic NLRP3 mutation exerts inflammasome-independent effects on the cardiac function remains unknown. We generated Nlrp3C257Y/WT knock-in mice as a novel CAPS model. Long-term survival, systemic inflammation, and cardiac function were assessed by biochemical, histological, and echocardiographic analyses. To determine inflammasome dependency, Nlrp3C257Y/WT mice were crossed with Asc-/- mice to generate double-mutant Nlrp3C257Y/WT × Asc-/- offspring. Nlrp3C257Y/WT mice exhibited early-onset cutaneous inflammation that gradually subsided, these mice developed marked left ventricular (LV) dilatation and mild systolic dysfunction after approximately 6 mo of age. Histological analysis revealed interstitial myocardial fibrosis in Nlrp3C257Y/WT mice. This result indicates that Nlrp3C257Y/WT mutation, which operates as a gain-of-function variant for inflammasome activation, impairs cardiac function largely driven by an inflammasome-dependent mechanism. In contrast, Nlrp3C257Y/WT × Asc-/- mice exhibited marked resolution of systemic inflammation; nevertheless, LV dilatation and reduced fractional shortening persisted. Long-term Nlrp3C257Y/WT mutation can lead to persistent cardiac dysfunction not only through inflammasome activation but also via inflammasome-independent mechanisms. Our findings reveal previously unrecognized inflammasome-independent mechanisms linking NLRP3 signaling to cardiac dysfunction. This study expands knowledge of the pathophysiological spectrum of CAPS and highlights inflammasome-independent NLRP3 signaling as a potential therapeutic target to prevent chronic cardiac complications in patients with CAPS and NLRP3-associated disorders.</p>","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":"215 10","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149220226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of natural killer cell depletion on innate and adaptive immune responses to COVID mRNA vaccination.","authors":"Allison Segard, Emilie Goguet, Hannah Haines-Hull, Kim C Williamson, Stephen K Anderson, Hooda Said, Mohamad-Gabriel Alameh, Edward Mitre","doi":"10.1093/jimmun/vkag266","DOIUrl":"10.1093/jimmun/vkag266","url":null,"abstract":"<p><p>This study assessed the role that natural killer (NK) cells play in a murine model of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Spike mRNA vaccination. Flow cytometric analyses revealed that mRNA vaccination results in recruitment and maturation of NK cells in the spleen. Primed (CD27+ CD11b+) NK cells increased from 0.35% of all CD45+ cells pre-vaccination to 2.44% at 4 d post-vaccination, while terminally mature (CD27- CD11b+) NK cells increased from 0.85% of all CD45+ cells pre-vaccination to 3.91% at 7 d post-vaccination. We next evaluated Spike mRNA and protein expression, circulating cytokines, and Spike-specific antibody and T cell responses in mice depleted of NK cells before primary or booster vaccination. Depleting NK cells prior to mRNA vaccination resulted in decreased serum levels of IL-1β and IL-6 at 6 and 24 h, respectively, after vaccination. NK depletion also caused a significant reduction in Spike mRNA expression in draining lymph nodes, with greater than 5-fold reductions in Spike mRNA copies/μL, as measured by digital droplet PCR. Three weeks post-vaccination with 1 μg mRNA LNP, Spike-specific CD25+ CD4 T cells were also significantly decreased. Despite these decreases in early pro-inflammatory cytokines, Spike mRNA expression, and Spike-specific CD4 T cells, NK depletion had little impact on Spike-specific antibody levels at 1 and 6 mo following single vaccination, as well as at 3 wk after booster vaccination. Together, these data suggest that NK cells contribute to early inflammatory responses induced by mRNA vaccination, yet their depletion does not impair the magnitude of long-term adaptive immune responses induced by this platform.</p>","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":"215 10","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13651638/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149147539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibition of cellular NEDDylation partially alters the MHC class I immunopeptidome.","authors":"Hooman Yari, Konstantin Divilov, Dylan T Fahey, Sofia A Arola, William H Hildebrand, Brian P Dolan","doi":"10.1093/jimmun/vkag258","DOIUrl":"https://doi.org/10.1093/jimmun/vkag258","url":null,"abstract":"<p><p>Determining how chemotherapeutic drugs alter the MHC class I-associated immunopeptidome is essential for designing rational combinatorial therapies to enhance antitumor CD8+ T-cell activity, such as immune checkpoint inhibitor Abs. We investigated the impact of a first-in-class inhibitor of cellular NEDDylation, MLN4924, on self-peptide presentation using 2 human tumor cell lines: HeLa cells secreting the human MHC class I protein HLA-A*11:01 and the glioblastoma cell line U87-MG. MLN4924 indirectly inactivates the cullin-RING ligases (CRLs), a large family of E3 ubiquitin ligases responsible for targeting numerous substrates for degradation by the ubiquitin-proteasome system. MLN4924 treatment prevented cell division and altered the transcriptome of HeLa cells in a predictable manner. However, MLN4924 treatment did not alter the cell-surface levels of MHC class I proteins. An analysis of the immunopeptidome and the source proteins, which yielded peptides for presentation, revealed some unexpected findings. Greater than 50% of the peptides presented, and more than two-thirds of the source proteins from which peptides were derived, remained unaltered after MLN4924 treatment. Furthermore, alterations to the transcriptome could not predict the observed changes to the immunopeptidome. Of the approximately 100 CRL substrates that were presented by HLA-A*11:01, most were presented independent of MLN4924 treatment. Alternative degradation pathways and the presence of intron sequences in the specific mRNA transcripts may help explain how these proteins yield peptides for Ag presentation. In summary, MLN4924 treatment only partially affects the immunopeptidomic profile, suggesting it could be used in combinatorial cancer immunotherapies.</p>","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":"215 10","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13653659/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149167907","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TCRαβ repertoire plasticity defines universal CD8+ T cell responses directed at influenza-specific HLA-A*02:01-PB1413-421 epitope.","authors":"Marios Koutsakos, Jeremy Chase Crawford, Ludivine Grzelak, Simone Rizzetto, Andrea T Nguyen, Priyanka Chaurasia, Jan Petersen, Louise C Rowntree, Emma Kaitlynn Allen, Steven Y C Tong, Allen C Cheng, Tom C Kotsimbos, Fabio Luciani, Jamie Rossjohn, Stephanie Gras, Paul G Thomas, Thi H O Nguyen, Katherine Kedzierska","doi":"10.1093/jimmun/vkag270","DOIUrl":"https://doi.org/10.1093/jimmun/vkag270","url":null,"abstract":"<p><p>HLA-A*02:01-restricted PB1413+CD8+ T cells provide the broadest reported cross-reactive immunity against influenza A, B, and C viruses. Here, we investigated T cell receptor (TCR) clonotypic signatures within these universal A2/PB1413+CD8+ T cell pools, compared with immunodominant influenza A-specific M158+CD8+ T cells and codominant influenza B-specific A2/HA543+CD8+ memory T cells. Using single-cell reverse transcriptase polymerase chain reaction and RNA sequencing methodologies, we defined TCRαβ repertoire composition and diversity. Our study shows that CD8+ T cells responding to these 3 epitopes differ in magnitude and TCRαβ repertoires in terms of gene usage and sharing, underpinned by specific TCR and structural features for each pMHC-I specificity. Our data demonstrated that the A2/PB1413+CD8+ TCRαβ repertoire encompassed diverse gene segment usage within both TCRα and TCRβ chains. These were, however, greatly variable across HLA-A2*02:01-expressing individuals and lacked any shared features within TRAV, TRBV, TRBJ, and TRAJ gene segments. This A2/PB1413+CD8+ TCRαβ diversity stemmed from the low probability of recombination attributed to a large number of N-insertions in the TCRβ chain. PB1413+CD8+ T cells also displayed remarkable plasticity in recognition of the A2/PB1413 epitope depicted by versatile CD8+ T cell recognition patterns of the universal A2/PB1413 epitope across HLA-A*02:01-expressing individuals. Conversely, TCRαβ repertoires within A2/BHA543+CD8+ and M158+CD8+ T cells displayed common TRAV, TRBV, TRBJ, and TRAJ gene segments, shared across HLA-A*02:01-expressing individuals and recognizing key residues within A2/BHA543 and A2/M158 epitopes. Overall, our data showed a great level of TCRαβ gene usage diversity within universal A2/PB1413+CD8+ T cells, indicating that the TCRαβ clonal plasticity defines universal immunity toward human influenza viruses.</p>","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":"215 10","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149207040","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TNFα promotes brain-predominant EAE independent of IFNγ and IL-17A in HLA-DR3 transgenic mice.","authors":"Ti-Ara J Turner, Stephanie R Peterson, Lian E Alt, Leeann S Aguilar Meza, David K Meyerholz, Shailesh K Shahi, Ashutosh K Mangalam","doi":"10.1093/jimmun/vkag268","DOIUrl":"https://doi.org/10.1093/jimmun/vkag268","url":null,"abstract":"<p><p>Multiple sclerosis (MS) is thought to be mediated by human leukocyte antigen (HLA) class II-restricted autoreactive CD4 T cells producing interleukin (IL)-17A and/or interferon γ (IFNγ), but the necessity of these cytokines for disease pathogenesis is unclear. Utilizing HLA-DR3 (DRβ1*0301) transgenic mice lacking IFNγ or IL-17A in experimental autoimmune encephalomyelitis (EAE), a model of MS, we found that neither cytokine is essential for disease induction, although both have distinct roles. The absence of IFNγ caused atypical, brain-predominant EAE characterized by high levels of IL-17A, while the absence of IL-17A resulted in classical EAE, targeting the spinal cord. To assess whether IL-17A drives atypical EAE in the absence of IFNγ, we generated HLA-DR3.IFNγ-/-.IL-17A-/- double knockout (DKO) mice. DKO mice developed atypical EAE with brain infiltration and inflammation of the brainstem and cerebellum, indicating that IL-17A is dispensable for brain-predominant disease in the absence of IFNγ. DKO mice exhibited significant CD4 T cell infiltration and increased expression of CD4 T cell-associated genes at peak disease. Prior to central nervous system infiltration, CD4 T cell accumulated in the spleen and inguinal lymph nodes of DKO mice, where they exhibited an altered cytokine milieu and upregulated genes involved in recruitment, activation, and migration to the brain. DKO mice exhibited elevated expression of tumor necrosis factor α (TNFα), granulocyte-macrophage colony-stimulating factor, and IL-17F; however, only TNFα inhibition ameliorated atypical disease. Together, our findings indicate TNFα promotes brain-predominant inflammatory pathology in the absence of IFNγ and IL-17A.</p>","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":"215 10","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149182418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Papaverine ameliorates psoriasis-like skin inflammation by regulating immune cell differentiation and RAGE-S100A7 axis in an imiquimod-induced murine model.","authors":"Nontaphat Leerach, Yupa Srithongchai, Seiichi Munesue, Kumi Kimura, Yu Oshima, Ai Harashima, Hisanori Goto, Mariko Tanaka, Pathitta Sakulsak, Hiroya Takahashi, Takahiro Ishimoto, Yoshimichi Sai, Yasuhiko Yamamoto","doi":"10.1093/jimmun/vkag233","DOIUrl":"https://doi.org/10.1093/jimmun/vkag233","url":null,"abstract":"<p><p>Psoriasis is a chronic, immune-mediated inflammatory skin disease affecting at least 2% of the global population. Papaverine, an alkaloid with known anti-inflammatory, anti-cancer, and RAGE-antagonistic properties, has not been previously evaluated for anti-psoriatic activity. This study investigated the protective effects and mechanisms of papaverine in an imiquimod (IMQ)-induced psoriasis-like model in BALB/c mice. Papaverine treatment significantly ameliorated clinical symptoms, as evidenced by reductions in psoriatic lesions, skin thickness, severity index scores, T- and B-cell infiltration, and cutaneous angiogenesis. It also downregulated IMQ-induced mRNA expression of keratinocyte differentiation markers Krt10 and Ivl. Flow cytometric analysis revealed a marked reduction in B220⁺CD138⁺ plasmablasts and B220⁻CD138⁺ plasma cells in both circulation and spleen. These effects were associated with modulation of key transcription factors involved in plasma cell differentiation, including Prdm1, Xbp1, and Bcl6. Notably, the population of CD3⁺CD4⁻CD8⁻ double-negative T cells was also decreased following papaverine administration. Inflammatory cytokine and chemokine mRNA levels in IMQ-exposed skin-namely Il1b, Il6, Ifng, Mcp1, Il22, S100a7, and Ager-were significantly suppressed. These findings suggest that papaverine ameliorates psoriasis-like symptoms through inhibition of proinflammatory cytokines and suppression of aberrant plasma cell differentiation. In conclusion, papaverine demonstrates therapeutic potential as a candidate for the treatment of psoriasis.</p>","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":"215 9","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148969397","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A skin-kidney neutrophil axis links ultraviolet exposure to renal angiogenesis and tissue remodeling in healthy and lupus kidneys.","authors":"Angelique Cortez, Lindsay K Mendyka, Alecia Roy, Joshua J Skydel, Lais Osmani, Paola Garcia, Elizabeth C Nowak, Akshaya Balasubramanian, Noelle N Kosarek, Fred W Kolling, Owen M Wilkins, Olivia F Brooker, Chinaza Nnam, Jason Pettus, Alessandra Celia, William F C Rigby, Vivekanand Tiwari, Christopher M Burns, Lucas A Salas, Michelle Petri, Andrea Fava, Sladjana Skopelja-Gardner","doi":"10.1093/jimmun/vkag178","DOIUrl":"10.1093/jimmun/vkag178","url":null,"abstract":"<p><p>Neutrophils have been implicated in mediating immune crosstalk between injured tissue and distal organs, either promoting local and distal inflammation or mediating tissue repair. Skin injury from ultraviolet (UV) light triggers neutrophil migration to the kidney, which may have implications for nephritis flares in systemic lupus erythematosus. Here, we demonstrate that after skin exposure to UV light, renal neutrophils upregulate proangiogenic transcriptional programs and activate renal endothelial angiogenesis and tissue remodeling processes in healthy kidneys. Ligand-receptor analysis identified Cd177-Pecam1 as a key neutrophil-endothelial interaction. In contrast to healthy control mice, skin exposure to UV light stimulated the expression of Tgfβ and Wnt signaling pathways in lupus-prone MRL/lpr mice. This tissue remodeling response was neutrophil dependent. Spatial transcriptomic analysis of lupus nephritis kidneys revealed that tissue remodeling and profibrotic pathways are highly expressed in neutrophil-rich areas. Neutrophil intrarenal levels were higher in the kidneys of lupus nephritis patients with active skin disease, compared with those without skin involvement at the time of the nephritis flare. Moreover, urinary neutrophils were increased in systemic lupus erythematosus patients with active skin disease, including sun-associated skin rash, even in the absence of lupus nephritis. These results support a model in which UV-triggered skin injury activates a neutrophil-mediated skin-kidney axis that promotes differential tissue remodeling pathways in healthy compared with lupus-prone kidneys.</p>","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":"215 9","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13532701/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148874210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Live versus killed Listeria monocytogenes immunization differentially programs Hup-specific CD4+ T cell responses with distinct protective outcomes.","authors":"Jessica Braverman, Ian R Monk, Minh Anh To, Nancy Wang, Timothy P Stinear, Linda M Wakim","doi":"10.1093/jimmun/vkag253","DOIUrl":"https://doi.org/10.1093/jimmun/vkag253","url":null,"abstract":"<p><p>The histone-like protein Hup is a highly conserved DNA-stabilizing and compacting protein found across bacterial families. We previously demonstrated that the Hup protein of Staphylococcus and Streptococcus species harbors a shared CD4+ T cell epitope, and that Hup77-88-specific CD4+ T cells confer cross-species protection against pulmonary infection with these bacteria. Here, we investigated whether exposure to the Gram-positive intracellular pathogen Listeria monocytogenes, that expresses an orthologous Hup protein, induces a Hup-specific CD4+ T cell response. Live L. monocytogenes infection in mice generated detectable but modest Hup78-89-specific CD4+ T cell responses. In contrast, immunization with heat-killed L. monocytogenes or infection with a listeriolysin O-deficient strain, induced robust Hup78-89-specific Th17 responses. Despite their expansion, heat-killed L. monocytogenes-induced Hup-specific CD4+ T cells did not protect against secondary L. monocytogenes challenge, consistent with the requirement for T helper 1 and CD8+ T cell immunity for anti-Listeria protection. However, these CD4+ T cells conferred protection against pulmonary infection with Staphylococcus aureus expressing the L. monocytogenes Hup epitope. These findings establish Hup as conserved CD4+ T cell antigen target across bacterial species and demonstrates that T cell polarization and pathogen lifecycle are critical considerations when designing pan-antibacterial vaccines targeting shared bacterial antigens.</p>","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":"215 9","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149074914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}