Getting on your last nerve: IFNs and resistance to infection

J Immunol. 2026 Jun 7;215(6):vkag169. doi: 10.1093/jimmun/vkag169. ABSTRACT Interferons (IFNs) affect almost all nucleated cells and induce transcriptional events that are associated with control of intracellular infections as well as regulatory pathways that influence inflammatory processes. How different hematopoietic and non-hematopoietic cell types interpret these signals is a reflection of cellular context and function. For … Read more

Antigen-presenting cancer-associated fibroblasts in murine pancreatic tumors differentially regulate T-cell phenotype and function

J Immunol. 2026 Jun 7;215(6):vkag165. doi: 10.1093/jimmun/vkag165. ABSTRACT Pancreatic ductal adenocarcinoma (PDAC) is characterized by an immunosuppressive tumor microenvironment (TME) in which cancer-associated fibroblasts (CAFs) play pivotal roles in shaping therapeutic responses. Among these, MHC-II-expressing antigen-presenting CAFs (apCAFs) modulate CD4 T-cell activity, yet their contribution to the antitumor immune response remains unclear. Using tumor clones … Read more

MHC class II on melanoma cells regulates the anti-tumor T cell response

J Immunol. 2026 Jun 7;215(6):vkag158. doi: 10.1093/jimmun/vkag158. ABSTRACT In human melanoma, tumor cell-specific MHC class II expression is associated with improved response to programmed death 1 and programmed death-ligand 1 blockade; yet the direct effect of melanoma cell-specific MHC class II expression on anti-melanoma T cell responses remains largely unknown. In the clinically relevant Yale … Read more

ENPP1-dependent USP2 ubiquitination governs SQSTM1-mediated autophagy-dependent ferroptosis in trophoblast cells and exacerbates placental dysfunction in gestational diabetes mellitus

J Immunol. 2026 Jun 7;215(6):vkag127. doi: 10.1093/jimmun/vkag127. ABSTRACT Downregulation of ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) has been implicated in autophagic cell death. However, how ENPP1 regulates the interplay between autophagy and ferroptosis to maintain trophoblast homeostasis in the context of gestational diabetes mellitus (GDM) remains unclear. To determine ENPP1’s role in autophagy-dependent ferroptosis and its contribution … Read more

ER stress amplifies inflammation via a dual mechanism involving IκBζ-XBP1s synergism and Regnase-1 degradation

J Immunol. 2026 Jun 7;215(6):vkag151. doi: 10.1093/jimmun/vkag151. ABSTRACT Inflammatory diseases arise from complex interactions between immune signaling and cellular stress. Although endoplasmic reticulum (ER) stress is a key modulator of immunity, the mechanisms by which it promotes inflammatory pathology remain incompletely understood. Notably, ER stress-induced NF-κB activation alone is insufficient to account for robust IL-6 … Read more

The V158F polymorphism in human FcγRIIIa/CD16a defines opposing receptor responses when interacting with soluble immune complexes

J Immunol. 2026 Jun 7;215(6):vkag160. doi: 10.1093/jimmun/vkag160. ABSTRACT The V158F polymorphism found in the human Fc receptor CD16a (also known as FcγRIIIa) is thought to influence autoimmune disorders and responses to IgG-based therapies. V158F is known to influence the IgG affinity, and thereby triggering of the CD16a receptor expressed on various immune cells. In contrast … Read more

Foxp1 controls Fezf2-dependent gene expression, mimetic mTEC diversity, and thymic central tolerance

J Immunol. 2026 Jun 7;215(6):vkag168. doi: 10.1093/jimmun/vkag168. ABSTRACT Forkhead Box P1 (Foxp1) is a transcription factor critical for the proper development of multiple tissues. While Foxp1 has a well-described role in regulating adaptive immunity through modulation of T and B cells, a function in medullary thymic epithelial cells (mTECs) has not been reported. Here we … Read more

MAPK-activated protein kinase 2 orchestrates memory T-cell inflation in cytomegalovirus infection

J Immunol. 2026 Jun 7;215(6):vkag170. doi: 10.1093/jimmun/vkag170. ABSTRACT Memory T-cell inflation is a distinctive immunological phenomenon observed during persistent viral infections such as cytomegalovirus (CMV). Unlike conventional memory T-cell responses, which contract after infection resolution, a subset of CMV-specific T cells undergoes a progressive and sustained expansion, termed “inflation”, which is thought to be critical … Read more

Genetic deletion of the inflammatory bowel disease-associated risk gene Rgs14 aggravates experimental colitis

J Immunol. 2026 Jun 7;215(6):vkag135. doi: 10.1093/jimmun/vkag135. ABSTRACT Regulators of G protein signaling (RGS) deactivate G proteins associated with G protein-coupled receptors (GPCRs), a large receptor family with diverse functions. Of the 20 RGS, the Rgs14 single-nucleotide polymorphism is associated with inflammatory bowel disease, and Rgs14 expression is higher in macrophages than in epithelial cells. … Read more

CSF1R-dependent macrophages control B cell development and function in the chicken immune system

J Immunol. 2026 Jun 7;215(6):vkag143. doi: 10.1093/jimmun/vkag143. ABSTRACT Acquired immunity in mammals depends upon capture and presentation of antigens by specialized macrophage populations in splenic marginal zone and lymph node sinuses and follicular dendritic cells within germinal centers. Cells referred to as follicular dendritic cells in chickens express CSF1R, the receptor for CSF1 and IL34. … Read more

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