The Journal of Immunology

Naive CD8 T cells undergo a discordant burst of cytokine production upon activation. Splenocytes from the indicated naïve TCR transgenic mice were activated in vitro with their cognate peptide antigen and IL-2 and IFN-γ production as well as the upregulation of CD25 and CD69 assessed at the indicated time points.

Data demonstrated that both IL-2-producing and non-producing CD8 T cells can establish a memory pool, and that memory formation could proceed independently of endogenous IL-2, but early intrinsic IL-2 reduced cell differentiation. Read more: https://ow.ly/ZOHF50Yn5rw.

In this #EditorsChoice, data from The Lund Lab show that CXCR6 promotes the adaptation of T cells as they engage antigen in tissue to increase the probability of survival, memory differentiation, and long-term residence.

🔗 https://ow.ly/6fjA50Yn5zf

Diagram showing IVIG inhibiting TNF-α in responsive KD but not in resistant KD, highlighting Myd88 and IκBζ roles in coronary artery endothelial cells.

Researchers found that dimethyl itaconate (DI) and dimethyl fumarate might suppress IVIG-resistant coronary artery inflammation in #kawasakidisease patients, highlighting their therapeutic potential for treating IVIG-resistant KD. https://ow.ly/CyFI50YnYGv.

Group of twelve people standing on green grass with trees and a hill in the background during daylight.

Data establish glutamine synthetase (GS) as a key regulator of CD8+ T cells’ stress resilience in the tumor microenvironment, and GS inhibition offered a promising therapeutic strategy to enhance immune-based cancer treatments. Read this #EditorsChoice: https://ow.ly/HoyV50Yn65q.

CD8+ lymphocytes exhibit a wide variety of functions, both pro- and anti-inflammatory, that contribute to control of Mycobacterium tuberculosis infection. A balance of these responses is required to achieve success on the level of the granuloma to prevent progression and dissemination, although there does not appear to be a single combination of cytokines that leads to containment. Created with BioRender.

In a #BriefReview, Joanne Flynn discusses the current understanding of roles for different CD8+ lymphocyte subsets in responses against Mycobacterium tuberculosis (Mtb) and implications for novel vaccine and therapeutic development. Read it here: https://ow.ly/9eZo50Yn61C

Diagram showing immune cell interactions in tumor environments with and without anti-PD-L1 therapy, highlighting T cell types and cytokine production.

Researchers established a preclinical platform for modeling cholangiocarcinoma (CCA) tumor-infiltrating lymphocyte (TIL) therapy, identifying a strategy that increases TIL efficacy and advances adoptive T-cell transfer development for solid tumors.

🔗 https://ow.ly/SbSj50YnYFr

Diagram showing TNF-α activating TNFR leading to IKB/NF-κB and AP1/NF-κB signaling, increasing MMP9 expression and chromatin acetylation in the nucleus.

Data show that ITE reduced TNF-α–induced matrix metalloproteinase 9 (MMP-9) expression via the H3K9 acetylation/NF-κB/AP-1 axis, highlighting a potential mechanism for mitigating MMP-9–related inflammatory disorders. Learn more: https://ow.ly/oGiG50YnYAz.

The Journal of Immunology invites applications for Section Editors, deadline March 31, 2026, with the American Association of Immunologists logo.

Are you passionate about the integrity of immunology research? We want you!

The Journal of Immunology is calling for new Section Editors. Influence the field and support your peers by applying to join our editorial board. Learn more and apply: https://ow.ly/O2p350YoHJq

#ScienceJobs #Immunology

Schematic of interactive components in AI and FCM. The bidirectional circle depicts an interactive process consisting of four critical elements that involves good experimental designs to generate high-quality datasets for the development and validation of robust AI models that can be applied to a wide range of applications, driving discovery, predictive diagnosis, reusable repository data, and generative innovations.

This month in Immunology Notes and Resources, researchers discuss applications of artificial intelligence in flow cytometry, focusing on overcoming challenges and identifying solutions. Read more in The JI: https://ow.ly/jlgZ50Yn6bc.

Card9 in Kupffer cells promotes liver damage in the initial phase. (A) Immunofluorescence analysis of liver sections from WT mice stained with anti-Card9 and anti-F4/80 antibodies. Scale bar: 20 μm. (B) Expression of Card9 in different cell types was examined via qPCR; genes are presented relative to the expression level of Gapdh. HC, hepatocyte; HSC, hepatic stellate cells; KC, Kupffer cells; LSEC, liver sinusoidal endothelial cell; NPC, nonparenchymal cell. (C) Card9 expression pattern in human liver cell subsets from Aizarani et al.32 (D) Schematic of the experimental design. The mice were i.v. injected with clodronate liposomes or PBS liposomes one day in advance; the mice were i.p. injected with 450 mg/kg of APAP, then blood samples were taken from the tail. (E) We performed F4/80 immunohistochemistry on clodronate-treated livers at 24 hours post–liposome injection.

Researchers identified the role of TREM2 receptors on Kupffer cells in orchestrating tissue damage during sterile inflammation. TREM2 receptors recognize components released upon cell death and operate as upstream signaling receptors. Read more: https://ow.ly/2urG50YnYxE.

Conceptual model illustrating the role of TTP in O3-induced ALI and inflammation. The resident airway epithelial and myeloid cells in the lung airspaces encounter inhaled O3, which triggers the release of proinflammatory cytokines/chemokines. In this process, TTP, an endogenous protein, modulates the post-transcriptional regulation of these proinflammatory mediators in a cell-specific manner. Our study demonstrates that the loss of TTP, whether systemic or cell-specific, can lead to an exaggerated inflammatory response. This is characterized by elevated levels of proinflammatory cytokines and neutrophil-specific chemoattractants, leading to worsened O3-induced ALI and inflammation. In contrast, systemic overexpression of TTP mitigates these effects by promoting the degradation of transcripts related to proinflammatory and neutrophil-specific chemoattractants.

Data indicate that enhancing tristetraprolin (TTP) expression could be a potential therapeutic strategy for targeting multiple inflammatory cytokines in ozone-induced acute lung injury and other inflammatory diseases. Learn more: https://ow.ly/h8Fj50YnYvK.

Graphical summary of Cutting Edge manuscript selection. Summary of manuscript editorial flow from submission to publication.

The JI is announcing important updates to the #CuttingEdge section to increase author flexibility, harness peer reviewers' expertise, and elevate the role of editorial curation in recognizing exceptional scientific advances. Learn more: https://ow.ly/x3yV50Yn6hU.

Proposed mechanism underlying human bystander CD8+ T-cell responses to innate immune signals. Innate stimuli cascade in monocytes could promote IL-2 secretion by monocytes and CD4+ T cells, which triggers bystander activation of CD8+ T cells.

Data demonstrated the pivotal role of IL-2 in mediating bystander responses of CD8+ T cells to innate stimuli, revealing a novel mechanism of immune response modulation during viral infection. Learn more: https://ow.ly/LT4S50Yn53k.

Pathways through a waypoint amino acid at position 55.

An #EditorsChoice article highlights models that enable detailed analysis of maturation pathway probabilities, helping researchers identify opportunities for the design of boosting immunogens to elicit HIV bnAb CH235.12 in a vaccination regimen. See more: https://ow.ly/woP950Yn54K

Vy2+ γδT17 development is perturbed in the neonatal period. (A) Bulk, Vγ2+, and Vγ4+ thymus cellularity in day 1–2 (D1–2) WT and RasGRP1 KO mice. (B) Proportion of γδ thymocytes in CD24/CD73 quadrants in D1–2 WT and RasGRP1 KO mice. (C) Proportion of γδ thymocytes producing IL-17 in D1–2 WT and RasGRP1 KO mice after 3 h PMA/IM stimulation. (D and E) Proportion of (D) IL-17+ γδ thymocytes that are Vγ2+, Vγ4+, or Vγ1.1+, or (E) percentage of Vγ2+, Vγ4+, or Vγ1.1+ γδ thymocytes that are IL-17+ in D1-2 WT and RasGRP1 KO mice after 3 h PMA/IM stimulation. Data are pooled from 2 independent experiments of 2–7 mice per experiment. **p < 0.01, ***p < 0.001, ****p < 0.0001.

Researchers defined the role of RasGRP1 in the development and effector programming of γδ T cells. RasGRP1 activation serves as an important signaling hub, which integrates signals from both non-TCR and TCR inputs to direct differentiation. Read more: https://ow.ly/rXll50Yn51v.

Microscopic image of immune cells stained in vibrant colors on the cover of The Journal of Immunology, February 2026 issue.

The latest issue of The Journal of Immunology is live! To learn more about current advancements in the field of #immunology, read the current issue today: https://ow.ly/zztM50Yn6ZI.

NR4A NRs display differential expression patterns from different subcellular locations in myeloid cells. (A–C) Monocytes, MDMs, AML cells, or HAMs were stained for DAPI (blue) and NR4A1, NR4A2, or NR4A3 (green). Representative confocal images from the different cell types are shown for (A) NR4A1, (B) NR4A2, and (C) NR4A3 from at least 100 monocytes/macrophages per experiment, representative of n = 3 experiments. Images were captured at ×20 magnification. Isotype control images are shown in Figs. S2–S4. Scale bar length is 50 μm. Insets are ×80 magnification.

Researchers identified the expression, location, and apoptotic activity of NR4A nuclear receptor family in human alveolar macrophages. Treatment of alveolar macrophage-like cells with NR4A ligands reduced M. tuberculosis growth. Learn more: https://ow.ly/MJAc50Yn4Xl.

Five people standing indoors in front of a commemorative plaque on a white wall, dressed in casual and semi-formal attire.

#EditorsChoice article from Dr. James McLaren, Systems Immunity Research Institute, suggests that S. aureus bloodstream infection in humans promotes a shift toward cells with greater IFN-γ–producing capacity, which may explain inflammation-driven disease pathogenesis.

🔗 https://ow.ly/KVfE50Ynbxr

Spatiotemporal dynamics of 2 different subsets of alternatively activated macrophages in tissue inflammation. (A) Tibialis anterior muscle was injected with cardiotoxin (CTX) to induce sterile tissue inflammation. Single-cell suspensions were analyzed by flow cytometry, and Uniform Manifold Approximation and Projection (UMAP) was performed on CD45+ CD11b+ myeloid cells. Combined UMAP plots (concat) from healthy (n=3) and inflamed muscle (n=3) show distinct populations annotated as resident mononuclear phagocytes (resMNP), infiltrating mononuclear phagocytes (inflMNP), polymorphonuclear neutrophils (PMN), and eosinophils (Eos). (B) Flow cytometric analysis of CD45+ CD11b+ myeloid cells showing representative UMAP plots at steady state and 2 d post-CTX-induced injury. Surface marker expression was visualized by overlaying fluorescence intensity heatmaps onto UMAP projections. Colors represent relative signal intensity, ranging from low (blue) to high (red).

Data show that distinct subsets of macrophages can acquire alternatively activated phenotypes in response to tissue injury, and these cellular subsets differentially contribute to the resolution of inflammation and tissue repair. Learn more: https://ow.ly/t1H850Yn4QK.

Extracellular HMGB1 impairs macrophage phagocytosis and promotes salivary gland dysfunction in Sjogren’s syndrome Abstract. Impaired phagocytosis of macrophages was observed in the salivary glands (SGs) of Sjogren’s syndrome (SS). This study aims to investigate the dyn

Data show that extracellular HMGB1 exacerbates the inflammatory-autoimmune microenvironments in salivary glands, suggesting that glycyrrhizin treatment may serve as a promising natural inhibitor for the management of Sjogren’s syndrome. Learn more: ow.ly/lp9S50YepSa.

NKG2A-mediated immune modulation of natural killer cells by Staphylococcus aureus Abstract. Natural killer (NK) cells are specialized lymphocytes that help protect against viruses and cancer. However, in the context of bacterial infectio

Data suggest that S. aureus bloodstream infection in humans promotes a phenotypic shift toward CD57− NKG2A+ NK cells with greater IFN-γ–producing capacity, providing a plausible way to promote inflammation-driven disease pathogenesis. Read more online: ow.ly/AEZA50Yepye.

Data identified a function of TLR7 in modulating myeloid-derived suppressor cells response to Candida albicans and suggested that RUNX1 and KLF4 were key transcription factors in regulating TLR7-mediated granulocytic MDSC immune responses. Learn more: ow.ly/qWfo50YepvI.

Data shed light on the immunological dimensions of hypoxia-inducible factor stabilization and its implications for patient care, urging further exploration of its therapeutic and safety profile. Learn more in The JI: ow.ly/sY2o50Yepq9

Deep phenomics of PRR agonist activated human blood Abstract. Human whole blood (WB) immunophenotyping may represent the in vivo immunological state with better fidelity than artificially isolated peripheral

Researchers used a deep phenomics modeling approach to elucidate the quantitative differences in major immune cell lineages in whole blood vs peripheral blood mononuclear compartments in a steady-state in vitro setting. See what they found: ow.ly/G6mv50YephG.

Distinct expression of CD56 and CD19 marks molecular and functional endotypes of tetanus- versus RBD-specific human bone marrow plasma cells Abstract. Plasma cell survival is influenced by various factors, including soluble mediators, intrinsic and extrinsic signals as well as adhesion molecules

Given the emerging potential of selective human bone marrow plasma cells subsets, data may provide a rationale for optimized vaccination protocols, as well as selective plasma-cell targeting in autoimmunity. Read why in The JI: ow.ly/nbqX50Yelj3.

Type 1 regulatory cells suppress T-cell cytotoxicity to alleviate liver injury during acute hepatitis B virus infection in mice Abstract. Hepatitis B virus (HBV) exclusively infects hepatocytes and produces large quantities of subviral particles containing its surface antigen (HBsAg

Researchers uncover the mechanisms that regulate T-cell responses to eliminate hepatitis B without causing immunopathology during acute infection, highlighting the critical function of Tr1 cells in modulating T-cell cytotoxicity. Read about it in The JI: ow.ly/bkYw50YeloL

Non-hematopoietic tryptophan metabolism is a driver of ineffective T cell responses during secondary pulmonary bacterial infection Abstract. Pulmonary infections often fail to produce long-lived immune memory and the underlying mechanism(s) for this are unclear. Given the complex inter

Crosstalk among cells of the lungs influences spatial organization of immune cells, affecting the ability to develop effective memory immune responses against bacterial infection and explaining the challenge of using live vaccines against tularemia.

🔗 ow.ly/X5x450Yelcr

The January issue of The Journal of Immunology is online now! Featuring updates on #CuttingEdge criteria and research from esteemed colleagues, be sure to give it a read.

🔗 bit.ly/TJI0126

Resolving the field: a role for Nod2 in T cells Abstract. NOD2 is primarily recognized as a cytosolic bacterial sensor of peptidoglycan, activating a downstream Rip2/NF-κB–mediated antimicrobial signalin

This #BriefReview highlights a T cell intrinsic role for NOD2 downstream of T cell receptor and co-receptor signaling and delineates how NOD2 shapes T cell responses in both homeostasis and disease. Read the full review: ow.ly/gKJs50Y4nNq.

TLR4al senses heme as a key damage/danger-associated molecular pattern to activate immune responses in lower vertebrates Abstract. Toll-like receptor 4 (TLR4), a critical pattern recognition receptor, detects microbe- and damage/danger-associated molecular patterns to trigger

#WeekendRead! #SameSameButDifferent! #FirstLove! Its discovery changed our understanding of the functioning of innate immunity and of the immune response in general, but actually not all TLR4s are equal, check this out @jimmunol.bsky.social 👇👇👇 academic.oup.com/jimmunol/art...