bims-cediti 2026-04-05 papers

bims-cediti

Biomed News

on Cell death in innate immunity, inflammation, and tissue repair

Issue of 2026–04–05
fourteen papers selected by
Kateryna Shkarina, Universität Bonn

The Yersinia pestis effector YopM binds the human pyrin death domain to inhibit inflammasome activation and effector-triggered immunity.
Upstream ORFs control TNFR1 abundance and tissue tolerance to TNF.
Microbial sensing through the non-canonical inflammasome modulates airway type 2 immunity.
β-alanine alleviates gout by inhibiting NLRP3 inflammasome activation.
Arrestin-3 scaffolds multiple MAP3Ks driving stress-induced JNK3 activation and cell death.
Nanoscale Mapping Reveals Periodic Organization of Neutrophil Extracellular Trap Proteins.
IAP-based biodegraders can convert necroptosis to apoptosis and eliminate cancer driving protein complexes.
A 3D model for assessing regulated cell death modalities.
STING causes replication stress and nascent DNA degradation via SAMHD1.
Electric dipole moment drives the dynamics of the TNFR1 complex I signalosome.
MDA5 generates compact ribonucleoprotein complexes via ATP-dependent double-stranded RNA unwinding.
Neuron-derived mitochondrial DNA (mtDNA) activates microglia via the Z-DNA binding protein 1 (ZBP1)-mediated pathway in mild traumatic brain injury.
Blood vessel-resident macrophages safeguard blood and vessel integrity in zebrafish.
Sulfated Glycosaminoglycans in Inflammation.

bioRxiv. 2026 Mar 25. pii: 2026.02.25.707193. [Epub ahead of print]

The Yersinia pestis effector YopM binds the human pyrin death domain to inhibit inflammasome activation and effector-triggered immunity.

Bethany W Mwaura, Adam R Simard, Morgan L Pettis, Ao Liu, Dean R Madden, James B Bliska.

Bacteria in the genus Yersinia use a type III secretion system to inject several effectors into host cells to disrupt multiple signaling processes. Two effectors disrupt host signaling by inactivating RhoA GTPases. Inactivation of RhoA triggers pyrin inflammasome assembly in infected phagocytes leading to a protective immune response. A third protein, YopM, is an essential virulence factor that counteracts effector-triggered immunity by inactivating pyrin. YopM has a leucine-rich repeat (LRR) domain and hijacks host kinases to inactivate pyrin by phosphorylation. Previously, the LRR domain of Yersinia pestis YopM was implicated in binding to an N-terminal region of human pyrin, which includes the eponymous pyrin domain (PYD), a member of the death domain family. However, the interaction mechanism was undefined. Using a bacterial two-hybrid assay, protein biochemistry and X-ray crystallography, we determined that the concave surface of the YopM LRR domain binds to the PYD. Identification of critical residues in the interaction revealed that YopM binds PYD R42, an amino acid important for positive and negative regulation of pyrin. Furthermore, we show that YopM codon substitution variants defective for PYD binding fail to inhibit the pyrin inflammasome in human monocytes infected with Yersinia . In addition, we found that PYD binding is dispensable for YopM to inhibit the inflammasome in murine macrophages, suggesting this effector uses a distinct mechanism to target mouse pyrin. These results define how Y. pestis YopM binds the human PYD and provide insights into how this interaction likely selected for pyrin gain of function variants resulting in the autoinflammatory disease Familial Mediterranean Fever.
SIGNIFICANCE: Pyrin is an inflammasome sensor encoded by the MEFV gene that is notable for its role in the autoinflammatory disease Familial Mediterranean Fever (FMF) and immunity to the plague agent Yersinia pestis . Y. pestis normally prevents inflammasome activation using the virulence factor YopM which binds pyrin and inhibits effector-triggered immunity. Gain of function mutations in MEFV that cause FMF were likely selected during historic plague pandemics to counteract YopM. Here, we defined the molecular mechanism of the YopM-pyrin interaction, which revealed that the effector binds to a key site of positive and negative regulation on the N-terminal death domain. These findings have important implications for understanding how YopM promotes pathogenesis and likely selected for gain of function mutations in MEFV.

DOI: https://doi.org/10.64898/2026.02.25.707193
Sci Immunol. 2026 Apr 03. 11(118): eaeb6484

Upstream ORFs control TNFR1 abundance and tissue tolerance to TNF.

Biao Ma, Wenxin Lyu, John Rizk, Xiaoyue Han, Majken Kjær, Vinnycius Pereira Almeida, Malin Jessen, Max Benjamin Sauerland, Carol Sze Ki Leung, Benoit J Van den Eynde, Xin Lu, Mads Gyrd-Hansen.

Tumor necrosis factor (TNF) orchestrates immune responses but can also drive inflammation-associated tissue damage. However, the mechanisms governing tissue tolerance to TNF remain poorly understood. Here, we reveal that TNF receptor 1 (TNFR1) abundance is regulated by two upstream open reading frames (uORFs) in the 5' untranslated region of TNFRSF1A and demonstrate that this is a key determinant of TNF tolerance. uORF2 dominantly limits TNFR1 translation, and its disruption increases TNFR1 levels, leading to excessive TNF-induced gene activation and cell death in cell culture. By contrast, uORF1 dynamically regulates TNFR1 levels in response to inflammatory and stress signals. In mice, uORF2 protects against TNF-driven systemic inflammatory response syndrome and liver pathology. We additionally report that the translation of other immune receptor messenger RNAs, including TLR4, IFNAR1, and IFNGR2, is also controlled by uORFs. Thus, regulation of TNFR1 levels and possibly of other immune receptors emerges as a mechanism safeguarding against excessive immune responses and tissue damage.

DOI: https://doi.org/10.1126/sciimmunol.aeb6484
Front Immunol. 2026 ;17 1784561

Microbial sensing through the non-canonical inflammasome modulates airway type 2 immunity.

Olivier Bernard, Sheyla Yamato, Oluwaferanmi Bello, Raquel Alvarez, Carter J Supple, Louis Z Sharp, Jahanvi Kumar, Maya E Kotas, Erin D Gordon.

   Introduction: Airway epithelial cells serve as critical sensors of both microbes and allergens, orchestrating immune responses through damage-associated molecular patterns including IL-33. Common aeroallergens induce type 2 inflammation through protease activity and pore-forming mechanisms that trigger epithelial IL-33 secretion and MAPK signaling. While microbial pattern receptors such as caspase-4 (which detects intracellular LPS) similarly generate membrane pores via the non-canonical inflammasome, it remains unknown whether these receptors can engage the same downstream epithelial IL-33 release and MAPK activation pathways.
Methods: Using human airway epithelial cell models, we examined caspase-4-dependent pyroptotic signaling downstream of intracellular LPS, including gasdermin D cleavage, IL-33 release, and MAPK-dependent transcriptional responses. We assessed the modulatory effect of protease allergen co-exposure on LPS-induced pyroptosis and interrogated the role of Orai1-mediated calcium signaling in vitro. In a mouse model of protease allergen challenge, we evaluated innate type 2 immune responses following genetic deletion of caspase-4 (formerly caspase-11). LPS preparations from multiple bacterial species were tested for capacity to engage the non-canonical inflammasome in epithelial cells, and publicly available human asthma datasets were analyzed for airway expression of caspase-4 and gasdermin D.
Results: Intracellular LPS activated caspase-4-dependent pyroptotic signaling, resulting in gasdermin D cleavage, IL-33 release, and MAPK-dependent transcriptional responses. Protease allergen exposure enhanced LPS-induced pyroptotic responses through Orai1-mediated calcium signaling in vitro. Genetic deletion of caspase-4 attenuated innate type 2 immune responses in the mouse protease allergen challenge model. LPS preparations from different bacterial species demonstrated variable capacity to engage the non-canonical inflammasome. Analysis of human asthma datasets revealed increased airway expression of both caspase-4 and gasdermin D in asthmatic patients relative to healthy controls.
Discussion: These findings identify the epithelial non-canonical inflammasome as a pathway capable of linking microbial pattern recognition to IL-33-dependent type 2 responses. This work establishes a mechanistic framework for understanding how bacterial sensing machinery may intersect with allergic inflammation during pathophysiological conditions, and suggests that caspase-4 signaling could represent a therapeutic target in asthma.

Keywords:  IL-33; lipopolysaccharides (LPS); non-canonical inflammasome; pyroptosis; type 2 immunity

DOI:  https://doi.org/10.3389/fimmu.2026.1784561
J Mol Cell Biol. 2026 Apr 01. pii: mjag004. [Epub ahead of print]

β-alanine alleviates gout by inhibiting NLRP3 inflammasome activation.

Xia-Ying Chen, Peng-Peng Zhu, Yuan Ying, Min-Yi Feng, Yu-Qin Xu, Liu-Bing Yu, Wen Xue, Yu Yu, Tao Li, Tao Zhou.

  The NLRP3 inflammasome plays a pivotal role in mediating pro-inflammatory cytokine release and inducing pyroptosis. Its aberrant activation is implicated in various inflammatory diseases, including gout, a condition characterized by monosodium urate crystal deposition in the ankle joint. Here, we identify β-alanine, an endogenous amino acid, as a novel NLRP3 inflammasome inhibitor with promising therapeutic potential for gout. Mechanistic investigations reveal that β-alanine binds to NLRP3, sequestering it within the trans-Golgi network. This interaction disrupts NLRP3 inflammasome assembly, thereby inhibiting the secretion of interleukin-1β (IL-1β) and IL-18. Moreover, in vivo experiments demonstrate that β-alanine administration significantly alleviates monosodium urate crystal-induced inflammation and joint swelling in mice without evident toxicity. Collectively, our findings not only uncover a novel endogenous regulatory mechanism for NLRP3-driven inflammation but also position β-alanine as a potential therapeutic candidate for gout.

Keywords:  NLRP3; gout; inflammasome; monosodium urate; β-alanine

DOI:  https://doi.org/10.1093/jmcb/mjag004
bioRxiv. 2026 Mar 09. pii: 2026.03.09.710604. [Epub ahead of print]

Arrestin-3 scaffolds multiple MAP3Ks driving stress-induced JNK3 activation and cell death.

Chen Zheng, Mohamed R Ahmed, Richard Sando, Vsevolod V Gurevich, Eugenia V Gurevich.

Non-visual arrestin-3 (a.k.a. β-arrestin-2) functions as a scaffold facilitating the activation of c-Jun N-terminal kinases (JNKs), an important pathway regulating cell fate. Here, we demonstrate that arrestin-3 scaffolds not only previously identified ASK1, but facilitates signaling by several MAP3Ks, including ZAKα, ZAKβ, MEKK1, and TAK1. We identified ZAK (sterile alpha motif and leucine zipper-containing kinase) as the predominant MAP3K mediating arrestin-3-dependent JNK3 signaling and chemotherapy drug-induced cell death in HEK293 cells. We also showed that a 16-residue-long arrestin-3-derived peptide binds ZAK and fulfills the scaffolding function of full-length arrestin-3, sensitizing cells to death induced by chemotherapy drugs. These findings demonstrate that arrestin-3 is a versatile facilitator of stress signaling and suggest that functional peptide mimics can be used therapeutically to facilitate drug-induced death of cancer cells.

DOI: https://doi.org/10.64898/2026.03.09.710604
Nano Lett. 2026 Apr 01.

Nanoscale Mapping Reveals Periodic Organization of Neutrophil Extracellular Trap Proteins.

Moritz Winkler, Till G A Mack, Britta J Eickholt, Jan Schmoranzer, Garth Lawrence Burn, Niclas Gimber.

  Neutrophils are essential cells of the innate immune system that release neutrophil extracellular traps (NETs) via NETosis. This specialized cell death pathway extrudes decondensed chromatin into the extracellular space. NET formation contributes to antimicrobial defense and coagulation, whereas dysregulated NETosis drives cancer, coagulopathy, and autoimmune diseases. Here we present a workflow combining optimized sample preparation, super-resolution imaging, and quantitative bioimage analysis to investigate the nanoscale organization of NETs. Our newly developed analysis tool, NanoNET, facilitates the NET protein binding pattern analysis. We identified specific NET proteins, including neutrophil elastase (NE) and proteinase 3 (PR3), that bind along DNA strands in a periodic fashion and are highly colocalized with nucleosomes, suggesting docking onto or around these structures. The workflow and analysis tools represent a significant methodological advance for studying protein distributions along NETs and filamentous structures in general. Understanding the NET filament organization is a critical step toward elucidating their formation and function.

Keywords:  Neutrophil extracellular traps; innate immunity; single-molecule localization microscopy; stimulated emission depletion microscopy; structured illumination microscopy; super-resolution microscopy

DOI:  https://doi.org/10.1021/acs.nanolett.5c05175
Cell Chem Biol. 2026 Mar 31. pii: S2451-9456(26)00075-9. [Epub ahead of print]

IAP-based biodegraders can convert necroptosis to apoptosis and eliminate cancer driving protein complexes.

Xiuquan Ma, François Vaillant, Deepagan Gopal, Kael Schoffer, Farzaneh Shojaee, Jiyi Pang, Christopher A Baldwin, James M Murphy, John Silke, Maria C Tanzer, Jane E Visvader, Ranja Salvamoser, James E Vince.

  Targeted protein degradation holds significant therapeutic potential. Intrabodies, such as nanobodies and monobodies, can degrade intracellular proteins via fusion to E3 ubiquitin ligases. Here, we developed multi-targeting biodegrader intrabodies using the RING domain of inhibitor of apoptosis (IAP) proteins, or the IAP-binding motif from Smac/DIABLO. When fused to monobodies recognizing the necroptosis effector mixed lineage kinase domain-like pseudokinase (MLKL), IAP-based intrabodies degraded both MLKL and IAPs, blocking necroptosis and sensitizing cells to apoptosis. The potent degradative ability of the IAP RING was demonstrated via fusion to distinct intrabodies, with those targeting RAS enabling IAP and RAS proto-oncogenes to be concurrently eliminated. Quantitative proteomics of select IAP-based intrabodies revealed additional degradation of the BAF chromatin-remodelling complex, uncovering IAP and BAF co-dependencies in cancer. This work establishes IAP-based intrabodies as a modular class of protein biodegraders, whose multi-targeting capacity can enable the redirection of damaging necrotic cell death toward apoptosis, and the eradication of cancer-drivers.

Keywords:  BAF; IAP; MLKL; PROTAC; SWI/SNF; Smac-mimetic; apoptosis; biodegrader; intrabody; necroptosis

DOI:  https://doi.org/10.1016/j.chembiol.2026.03.005
Methods Cell Biol. 2026 ;pii: S0091-679X(25)00098-6. [Epub ahead of print]204 81-92

A 3D model for assessing regulated cell death modalities.

Robin Demuynck, Dmitri V Krysko.

  Three-dimensional (3D) models more closely represent the in vivo situation and are therefore more relevant models for drug screening. Among the more than twelve regulated cell death (RCD) modalities, immunogenic cell death (ICD) stands out for its ability to initiate efficient anti-tumor immune response. For example, ferroptosis, which can be induced via the inhibition of GPX4 leading to uncontrolled lipid peroxidation, might be immunogenic under certain conditions. It is crucial to identify which cell death modality is induced, as certain cancer types exhibit resistance to specific forms of cell death. However, a major limitation of 3D models is the lack of high-throughput assays, which often require dissociation of the 3D models, potentially leading to misinterpretation of results. Here, we describe a protocol for identifying and quantifying the induction of RCD modalities in 3D models, such as spheroids. This method eliminates the need for tumor spheroid dissociation and is compatible with other screening techniques, including confocal microscopy. This protocol enables high-throughput screening of various cell death inducers in intact 3D models, serving as a crucial first step in the identification of novel inducers and their specificity for particular ICD and RCD types.

Keywords:  Cancer; Cell death assay; Ferroptosis; Immunogenic cell death; Immunotherapy; Multimode plate reader; Regulated cell death; Spheroids

DOI:  https://doi.org/10.1016/bs.mcb.2025.03.017
bioRxiv. 2026 Mar 28. pii: 2026.03.28.714577. [Epub ahead of print]

STING causes replication stress and nascent DNA degradation via SAMHD1.

Barbara Teodoro-Castro, Rafael Cancado de Faria, Elena V Shashkova, Atika Malique, Madison B Adolph, Lilian N D Silva, Susana Gonzalo.

STING is a key innate immune adaptor, classically activated by cytosolic DNA via cGAS-cGAMP to induce type I interferon signaling. While its cytoplasmic role is well defined, recent studies reveal that STING participates in non-canonical signaling pathways and localizes at the nuclear envelope and chromatin, where its functions remain poorly understood. In Hutchinson Gilford Progeria Syndrome (HGPS), a premature aging disease caused by expression of lamin A mutant protein named progerin, STING accumulates in the nucleus and drives chronic inflammation. Here, we show that replication stress (RS) is a trigger of STING nuclear accumulation and binding to chromatin. In addition, we uncover a previously unrecognized role for nuclear STING binding to nascent DNA and promoting RS in progeria and tumor cells. Mechanistically, STING contributes to replication fork slowing and stalling by limiting dNTPs availability. In addition, STING hinders replication fork protection/stability upon stalling, by facilitating MRE11-mediated nascent DNA degradation (NDD). We also find that STING contribution to depletion of dNTPs and NDD is mediated by SAMHD1. As such, SAMHD1 knockdown phenocopies STING abrogation in progeria cells and rescues replication fork speed and stability in STING-overexpressing tumor cells. These findings define a pathological STING-SAMHD1 axis that drives RS and genome instability in both progeria cells and tumor cells with elevated STING activity, uncovering a feedforward loop between innate immune signaling and impaired DNA replication.
Highlights: Replication stress in human fibroblasts triggers STING nuclear accumulation and an IFN responseSTING upregulation and nuclear accumulation hinders replication in progeria fibroblasts and U2OS tumor cellsSTING-induced replication stress features fork slowing/stalling and nascent DNA degradationSTING-induced fork slowing/stalling is mediated by the dNTPase SAMHD1SAMHD1-enabled MRE11 activity is responsible for STING-induced nascent DNA degradation.

DOI: https://doi.org/10.64898/2026.03.28.714577
Nature. 2026 Apr 01.

Electric dipole moment drives the dynamics of the TNFR1 complex I signalosome.

Jianping Liu, Jing Zhao, Jiayang Gao, Kun Zhao, Yaoyao Han, Jing Yang, Zefei Li, Jianyu Ye, Ziyu Sun, Fengyi Wang, Xinyi Liu, Zekai Li, Siyu Ji, Bo Liu, Cong Liu, Yixiao Zhang, Junying Yuan, James J Chou.

Dynamic assembly of the complex I signalosome mediated by three death domain (DD)-containing proteins-TNFR1, TRADD and RIPK1-is key for transmitting extracellular TNF stimuli to intracellular NF-κB signalling in controlling 'live or die' cell fate1. This signalling hub features the rapid recruitment of TRADD and RIPK1 after engagement of TNFR1 by TNF for the formation of complex I, followed by timed disassembly for transition into downstream signalling complexes2,3, but the mechanism driving the dynamic reversibility of complex I remains unclear. Here we captured the assembly core of complex I and determined its cryo-electron microscopy structure, showing a pentameric fibre comprising 31 DDs, with a single layer of a TRADD-DD pentamer sandwiched between multiple layers of TNFR1-DD and RIPK1-DD homopentamers. Structural analysis revealed a strong opposing electric dipole moment (EDM) generated by RIPK1-DD oligomerization relative to that of TNFR1-DD and TRADD-DD. Structure-guided mutagenesis in TNFR1-TRADD-RIPK1 pentameric fibres altering the EDM without affecting DD oligomerization demonstrated the role and mechanism of EDM in driving the dynamic reversibility mediating the rapid assembly and disassembly of complex I. Our study demonstrates a role for long-range interactions mediated by protein EDMs in driving the assembly and disassembly of super-signalling complex I for promoting NF-κB signalling.

DOI: https://doi.org/10.1038/s41586-026-10304-1
Nucleic Acids Res. 2026 Mar 19. pii: gkag274. [Epub ahead of print]54(6):

MDA5 generates compact ribonucleoprotein complexes via ATP-dependent double-stranded RNA unwinding.

Salina Quack, Sourav Maity, Pim P B America, Misha Klein, Alba Herrero Del Valle, Rahul Singh, Joe D Joiner, Zainab M Rashid, Quinte Smitskamp, Paula Rivas, Flavia S Papini, Chase P Broedersz, Wouter H Roos, Yorgo Modis, David Dulin.

Long double-stranded RNA (dsRNA) in the cytosol acts as a potent inflammatory molecule recognized by the receptor MDA5, triggering the innate immune response. Mutations affecting MDA5 ATPase activity lead to severe pathological conditions. MDA5 nucleoprotein filament assembly-disassembly dynamics are proposed to regulate dsRNA recognition, though the exact mechanism remains unclear. Here, we employed magnetic tweezers to monitor the assembly and manipulate MDA5 filaments at the single dsRNA level. Following a slow nucleation event, MDA5 assembles cooperatively and directionally into (partial) filaments and utilizes ATP hydrolysis to compact dsRNA through unwinding into single-stranded RNA (ssRNA), even against a significant opposing force. This compacted state is further stabilized by oligomerization of the caspase recruitment domain of MDA5 and requires high force to be disrupted. ssRNA gaps impaired compaction, suggesting a new mechanism for dsRNA recognition. We propose that MDA5-mediated dsRNA compaction captures viral dsRNA, preventing further usage for viral replication.

DOI: https://doi.org/10.1093/nar/gkag274
Proc Natl Acad Sci U S A. 2026 Apr 07. 123(14): e2527009123

Neuron-derived mitochondrial DNA (mtDNA) activates microglia via the Z-DNA binding protein 1 (ZBP1)-mediated pathway in mild traumatic brain injury.

Michela Marcatti, Javier Allende Labastida, Tony Zifeng Tang, Akbar Ahmad, Christina Payne, Nora Schwartz, Paula Villarreal, Olivia D Solomon, Gracie Vargas, Ping Wu, Bartosz Szczesny.

  Traumatic brain injury (TBI) is a leading cause of morbidity and mortality, with closed-head mild TBI (mTBI) accounting for nearly 90% of all cases. Early pathological events include microglial activation and neuronal mitochondrial dysfunction; however, their interconnection in mTBI remains poorly understood. Using a clinically relevant closed-head weight-drop mouse model, we identified mitochondrial DNA (mtDNA)-specific damage and increased expression of innate inflammatory markers (IL-1α/β, IL-6, TNFα, and CXCL1) in the cerebral cortex during the acute mTBI phase. Mechanistically, neurons subjected to in vitro injury model of mTBI exhibited early mtDNA-specific damage followed by mtDNA release via extracellular vesicles (EVs) together with the neuronal and exosomal markers. The released neuronal mtDNA induced a robust microglial activation mediated by binding to the cytoplasmic DNA/RNA sensor Z-DNA-binding protein 1 (ZBP1), triggering activation of the ZBP1-TBK1-IRF3 pathway resulted IL-6 and TNFα expression. An early, enhanced amounts of mtDNA, neuronal and exosomal markers were measured in EVs circulating in the blood of mice subjected to mTBI. ZBP1 knockout (KO) mice displayed suppressed microglial-but not astrocytic-activation in the cortex during the acute mTBI phase. We also measured accumulation of mtDNA-specific damage in the hippocampus during the postacute mTBI phase. The absence of microglial activation in ZBP1 KO mice exacerbated hippocampal-related memory deficits in the postacute mTBI phase. Collectively, our findings identify mtDNA-ZBP1 signaling as a key mechanism regulating microglial activation in mTBI.

Keywords:  Z DNA binding protein 1; microglia; mild traumatic brain injury; mitochondrial DNA; neuroinflammation

DOI:  https://doi.org/10.1073/pnas.2527009123
Nat Immunol. 2026 Mar 31.

Blood vessel-resident macrophages safeguard blood and vessel integrity in zebrafish.

Bart Weijts, Jeroen A A Demmers, Catherine Robin.

Tissue-resident macrophages populate nearly all organs, where they adopt tissue-specific roles essential for immune defense, tissue development and homeostasis. Their dysfunction contributes to inflammation, cancer and other diseases. Whether a dedicated macrophage population operates within the extensive vascular network, one of the body's largest and most widely distributed tissues, has remained unknown. Here, using high-resolution spatiotemporal live imaging in zebrafish embryos, we identify a distinct population of macrophages residing within blood vessels, termed blood vessel-resident macrophages (bMΦs), with conserved features in mice. bMΦs patrol the bloodstream, clear foreign particles and unfit cells, and act as first responders to endothelial damage. bMΦs emerge directly from axial vessels through an atypical endothelial-to-macrophage transition that is independent of Runx1 and Csf1r. Our findings reveal a previously unrecognized macrophage population dedicated to vascular immune surveillance, uncovering mechanisms that preserve blood and vessel integrity and offering potential therapeutic avenues for bloodborne and vascular diseases.

DOI: https://doi.org/10.1038/s41590-026-02481-y
Adv Exp Med Biol. 2026 ;1491 221-231

Sulfated Glycosaminoglycans in Inflammation.

Satomi Nadanaka, Hiroshi Kitagawa.

  Inflammation has long been regarded as a tissue repair mechanism activated by the body in response to infection or tissue injury. In recent years, chronic inflammation has been implicated as a proinflammatory factor not only in various diseases, such as cancer, atherosclerosis, obesity, and Alzheimer's disease, which increase with age, but also in the aging process itself. What mechanisms cause the inflammatory response that normally dissipates, persists, and becomes chronic? Elucidating the factors that cause chronic inflammation and the mechanisms that induce it will provide insights into the prevention and control of various age-related diseases. In this review, we focus on proteoglycans as factors that cause chronic inflammation and discuss proteoglycans as DAMPs that cause inflammation.

Keywords:   DAMPs; Glycosaminoglycan; Heparan sulfate; Inflammation; Proteoglycan; Chondroitin sulfate

DOI:  https://doi.org/10.1007/978-3-032-04153-1_14