Ask about this productRelated genes to: CLAN antibody
- Gene:
- NLRC4 NIH gene
- Name:
- NLR family CARD domain containing 4
- Previous symbol:
- CARD12
- Synonyms:
- CLAN1, ipaf, CLANA, CLANB, CLANC, CLAND, CLR2.1, CLAN
- Chromosome:
- 2p22.3
- Locus Type:
- gene with protein product
- Date approved:
- 2002-09-19
- Date modifiied:
- 2019-04-23
Related products to: CLAN antibody
Related articles to: CLAN antibody
- The innate immune system serves as the primary barrier against viral invasion, utilizing pattern recognition receptors (PRRs) to orchestrate a rapid defense. Among these, the nucleotide-binding domain and leucine-rich repeat (NLR) containing proteins function as central signaling scaffolds, assembling into multiprotein complexes known as inflammasomes. These complexes drive the maturation of pro-inflammatory cytokines IL-1β and IL-18, and initiate gasdermin D (GSDMD)-mediated pyroptosis, a lytic cell death pathway that eliminates intracellular replication niches. This comprehensive review synthesizes the diversified landscape of inflammasome activation during viral infections, extending beyond the canonical NLRP3 inflammasome to include specialized sensors such as NLRP6, NLRP9, NLRP1, NLRP12, and NLRC4. We critically evaluate the evolutionary "arms race" between host defenses and viral pathogens, detailing the sophisticated immune evasion strategies employed by viruses-ranging from the expression of decoy proteins and direct proteolytic cleavage of immune sensors to the manipulation of post-translational modifications (PTMs). Furthermore, we discuss the dual nature of inflammasome activation, which balances protective viral clearance against pathological hyperinflammation, and provide an exhaustive analysis of novel therapeutic strategies, including direct NLR inhibitors and downstream cytokine blockers, currently navigating clinical transition. - Source: PubMed
Publication date: 2026/05/08
Hou ShiyuanShen XingSun DanniAn YulinZhou YuxuanSun XingWang ShuhanLiu XinyueZhu MengtingZhao ShuaiLiu ZiyuWu XinganLiu Rongrong - Pyroptosis, NLRC4 and mitochondrial calcium uniporter (MCU)'s role in spinal cord ischemia/reperfusion injury (SCIRI) remain unclear. The role of exosomal piRNAs in SCIRI is underexplored. We aimed to investigate the neuroprotective effects of exosomes obtained from bone marrow mesenchymal stem cells (BMSCs) overexpressing piR-161382 in SCIRI. - Source: PubMed
Publication date: 2026/05/22
Tong XiangyiMa QingAn GuihangZhu XinzhuJia PeiwenMa HongChen Fengshou - The aberrant activation of the NOD-like receptor protein 3 (NLRP3) inflammasome has been implicated in the pathogenesis of various human inflammatory diseases. Although a wide variety of NLRP3 inflammasome inhibitors have been developed, no drug targeting the NLRP3 inflammasome has been approved for use in clinical settings. In this study, we identified ciclopirox olamine (CPX), an antifungal agent approved by the US Food and Drug Administration (FDA), as a novel NLRP3 inflammasome inhibitor. CPX specifically blocks NLRP3 inflammasome activation but not AIM2, NLRC4, Pyrin, NLRP1, or NLRP6 inflammasomes. Mechanistically, CPX directly disturbs NLRP3 inflammasome assembly by inhibiting NLRP3 oligomerization. Furthermore, CPX binds to the NACHT domain of NLRP3 at Y381 and reduces NLRP3 ATPase activity, thereby blocking NLRP3 oligomerization. More importantly, CPX administration notably exerts therapeutic effects on mouse models of sepsis, colitis, and metabolic disorders. CPX is also active ex vivo in cells from healthy individuals or patients with gout. Taken together, our results demonstrate that CPX acts as an NLRP3 inflammasome inhibitor and is a promising therapeutic agent for NLRP3 inflammasome-associated diseases. - Source: PubMed
Publication date: 2026/05/19
Xia XinyuYou HuiZhang KeJiang HuiLiu HongpingLiu LianghuaZhang AijieZhou You - As a leading cause of severe pulmonary infections, such as hospital-acquired pneumonia, (PA) poses a significant threat to public health. Macrophage polarization plays a central role in the control of PA infection; however, its precise regulatory mechanisms remain to be fully elucidated. It remains unclear whether MERTK participates in the regulation of macrophage polarization induced by PA infection, as well as its potential downstream molecular mechanisms, especially the association with the NLRC4 inflammasome. This study was designed to investigate the specific role and underlying molecular mechanisms of MERTK-mediated macrophage phenotypic switching during PA infection, with the goal of defining the MERTK-NLRC4 macrophage polarization regulatory axis. The expression dynamics of MERTK in alveolar macrophages from PA-infected mice were detected via Reverse transcription quantitative real-time PCR (RT‑qPCR) and Western blotting (WB). Flow cytometry was employed to determine the proportions of M1 (CD86+F4/80+) and M2 (CD206+F4/80+) macrophages. ELISA was utilized to quantify the levels of M1-associated (TNF-, IL-6) and M2-associated [IL-10, transforming growth factor (TGF)-] inflammatory cytokines, while the phagocytic activity of macrophages against PA was detected. WB was further applied to detect the expression of cleaved caspase-1 and N-GSDMD in the NLRC4 inflammasome pathway. The secretion of IL-1 and IL-18 and the release of lactate dehydrogenase were assessed. PA infection induced the upregulation of MERTK in alveolar macrophages. MERTK knockdown facilitated macrophage polarization toward the M1 phenotype while suppressing M2 polarization. Mechanistically, MERTK knockdown impaired NLRC4 inflammasome activation. Functional rescue experiments validated that MERTK overexpression activated M2 polarization by activating NLRC4 inflammasomes, which was reversed by NLRC4 knockdown. By upregulating MERTK to activate NLRC4 inflammasomes, PA facilitated M2 polarization of alveolar macrophages. This discovery furnished a critical theoretical foundation for the development of novel therapeutic strategies for PA infection targeting the MERTK-NLRC4 inflammasome-macrophage polarization axis. - Source: PubMed
Chen RongXu Yuanyuan - Rheumatoidarthritis (RA) is an autoimmune disease accompanied by joint swelling,stiffness, and pain, leading to a sharp decline in quality of life. However,the treatment of RA still faces numerous challenges. Clinical studies indicatethat specific hypoglycemic agents alleviate the symptoms of RA, while the potentialmolecular mechanism remains unknown. Herein, we initially assess the efficacyof various categories of anti-diabetic medications including biguanides, GLP1R(glucagon like peptide 1 receptor) agonists, SLC5A2/SGLT2 (solute carrierfamily 5 member 2) inhibitors, DPP4 (dipeptidyl peptidase 4) inhibitors,sulfonylureas, thiazolidinediones, and insulin analog in RA models ofcollagen-induced arthritis (CIA) and serum-transfer arthritis (STA). Resultsdemonstrate that solely thiazolidinediones (pioglitazone [PIOG]) confersuperior efficacy, whereas the other anti-diabetic agents provide minimal or notherapeutic benefits. Mechanistically, thiazolidinediones (PIOG) activatesPPARG/PPARγ (peroxisome proliferator activated receptor gamma) to promotemitophagic flux, thereby inhibiting aberrant NLRP3 inflammasome activation andreducing pro-inflammatory factors IL1B/IL1-BETA (interleukin 1 beta) and IL18 (interleukin18) release. Notably, loss of autophagy either genetically or pharmacologicallysubstantially diminishes the anti-inflammatory effects of PIOG both in vitroand in vivo. In summary, these results offer new mechanistic insight intodisease crosstalk and support the translational value of thiazolidinedionesPIOG as a candidate for precision therapy in RA or multimorbidity of RA and type2 diabetes mellitus (T2DM). 3-MA: 3-methyladenine; ACP5/TRAP: acid phosphatase 5, tartrate resistant; AIM2: absent in melanoma 2; ALUM: aluminum hydroxide adjuvant; ANOVA: analysis of variance; PYCARD/ASC: PYD and CARD domain containing; ATP: adenosine triphosphate; BMDM: bone marrow-derived macrophage; BV:TV: bone volume:tissue volume; CIA: collagen-induced arthritis; DAPI: 4',6-diamidino-2-phenylindole; DNA: deoxyribonucleic acid; ELISA: enzyme-linked immunosorbent assay; FG: Fast Green; GFP: green fluorescent protein; GSDMD: gasdermin D; IL1B/IL1-BETA: interleukin 1 beta; IL18: interleukin 18; LDH: lactate dehydrogenase; LPS: lipopolysaccharide; Micro-CT: micro-computed tomography; MSU: monosodium urate; mtDNA: mitochondrial DNA; mtROS: mitochondrial reactive oxygen species; NAC: N-acetylcysteine; NLRP1B: NLR family, pyrin domain containing 1B; NLRP3: NLR family, pyrin domain containing 3; NLRC4: NLR family, CARD domain containing 4; OGTT: oral glucose tolerance test; PBS: phosphate-buffered saline; PINK1: PTEN induced putative kinase 1; PIOG: pioglitazone; PPARG/PPARγ: peroxisome proliferator activated receptor gamma; RA: rheumatoid arthritis; ROS: reactive oxygen species; STA: serum transfer arthritis; STZ: streptozotocin; T2DM: type 2 diabetes mellitus; Tb.N: trabecular number; Tb.Sp: trabecular separation; Tb.Th: trabecular thickness; THP-1: human monocytic leukemia cell line; TNF/TNF-α: tumor necrosis factor; TOMM20: translocase of outer mitochondrial membrane 20. - Source: PubMed
Publication date: 2026/05/25
Fu TingtingWu YanglinWang BoZhang QinGuo LujunHan ZezhangCao JiaLin Jun