Ask about this productRelated genes to: MadCAM1 antibody
- Gene:
- MADCAM1 NIH gene
- Name:
- mucosal vascular addressin cell adhesion molecule 1
- Previous symbol:
- -
- Synonyms:
- MACAM1
- Chromosome:
- 19p13.3
- Locus Type:
- gene with protein product
- Date approved:
- 2000-02-11
- Date modifiied:
- 2014-11-19
Related products to: MadCAM1 antibody
Related articles to: MadCAM1 antibody
- This first-in-human study evaluated the safety, pharmacokinetics (PK), food effect, and pharmacodynamics (PD) of AJM347, a novel orally active, selective α4β7 integrin antagonist, in healthy Caucasian and Japanese adult males. The study consisted of three parts. In the single-ascending dose (SAD) study (Part 1), AJM347 was administered in doses ranging from 6 to 2420 mg. The effect of food was evaluated in Part 2. In the multiple-ascending dose (MAD) study (Part 3), AJM347 was administered twice daily (200-800 mg) for 7 days. Single and multiple oral doses of AJM347 were safe and well tolerated. No changes in lymphocyte counts in whole blood and cerebrospinal fluid were observed. AJM347 was rapidly absorbed and the active metabolite, CAN2281, was rapidly formed. Administration of AJM347 after meals achieved higher trough concentrations of CAN2281 compared with administration under fasted conditions. AJM347 rapidly and dose-dependently inhibited mucosal addressin cell adhesion molecule-1 binding to CD4+ T cells. Doses ≥200 mg twice daily maintained >90% inhibition (α4β7 receptor occupancy) for up to 24 h. PD effects correlated well with plasma concentrations of the active metabolite CAN2281. AJM347 demonstrated a favorable safety profile, effective target engagement, and promising PK properties for oral administration. The timing of dosing relative to meals did not affect the safety or overall PK profiles, but postprandial administration led to higher trough concentrations, suggesting that dosing after meals may represent the optimal regimen for the continued clinical development of AJM347. Blood samples were collected to assess PK and PD (α4β7 receptor occupancy). Samples were also collected to measure lymphocyte counts in peripheral blood and cerebrospinal fluid (CSF). - Source: PubMed
Koyama TetsuyaSeki Tatsunori - Integrin α4β7 is a key adhesion receptor that mediates lymphocyte homing to the intestinal mucosa through interactions with MAdCAM-1, VCAM-1, and fibronectin, thereby playing a central role in gut immune surveillance and mucosal immunity. Emerging evidence has expanded its functional scope beyond intestinal homeostasis to encompass diverse inflammatory and metabolic diseases. This review systematically summarizes the structural characteristics, ligand interactions, and conformational regulation of α4β7, with an emphasis on its pathogenic roles in inflammatory bowel disease, cardiovascular diseases, diabetes, liver disorders, autoimmune diseases, gastrointestinal malignancies, HIV infection, asthma, and graft-versus-host disease. We discuss the underlying mechanisms, including lymphocyte trafficking, T cell co-stimulation, immune subset dysregulation, and crosstalk with the gut microbiota and epithelial barrier. In addition, we review the current landscape of α4β7-targeting therapeutics, including vedolizumab, etrolizumab, ontamalimab, and small-molecule antagonists, highlighting their clinical applications and limitations. By integrating recent mechanistic insights and therapeutic advances, this review provides a comprehensive framework for understanding the multifaceted roles of α4β7 and informs future strategies for targeting this integrin in disease. - Source: PubMed
Publication date: 2026/08/05
Chen YueChen YongZhang ZhiyuanTao MengxingGeng Chi - Memory-phenotype (MP) CD4 T lymphocytes develop from peripheral naive precursors via self-recognition at homeostasis. While MP cells exert innate immune function in infectious and autoimmune contexts, their functional significance in ischemia-reperfusion injury (IRI) remains unclear. Here we show that blood-circulating MP lymphocytes rapidly infiltrate the gut in the absence of antigen recognition during intestinal IRI. This MP migration is directed by αβ that binds to vascular MAdCAM-1, with the latter's expression immediately upregulated by IRI-induced TNF-α. Once accumulated in the gut, MP cells respond to IL-12 to produce IFN-γ that elevates CXCL1 and CXCL2 levels and orchestrates neutrophils, thereby exaggerating tissue injury. Furthermore, such innate MP responses are operative in hepatic but not renal IRI. Together, our results reveal blood-circulating MP cells as a unique innate amplifier of IRI that rapidly accumulates in the gut to exacerbate tissue injury via neutrophil orchestration. - Source: PubMed
Publication date: 2026/07/29
Sato KosukeTayama ShunichiKawajiri AkihisaLi JingYang ZiyingMitsuwaka RyojiGao FengAsami NatsukiAoki ReokaNagashima HiroyukiMatsuda KenshiroNakahashi-Oda ChigusaIwakura YoichiroShibuya AkiraWada MotoshiIshii NaotoKawabe Takeshi - Gut dysbiosis compromises cancer immunosurveillance by downregulating ileal mucosal addressin cell adhesion molecule 1 (MAdCAM-1), but the metabolic landscape associated with gut dysbiosis remains elusive. Here, we show that antibiotics (ABX) or ABX-associated Enterocloster species lead to the loss of secondary bile acids (BAs) including deoxycholic acid (DCA) and the accumulation of tauro-conjugated primary BAs (tauro-chenodeoxycholic acid [TCDCA] and tauro-β-muricholic acid [T-βMCA]) from the alternative pathway in the plasma of patients and mice. Fecal microbial transplantation (FMT), the ileum-specific farnesoid X receptor (FXR) agonist fexaramine, or glycodeoxycholic acid (GDCA) compensated dysbiosis-associated BA abnormalities and circumvent primary resistance to PD-1 blockade. GDCA curtailed ABX-induced MAdCAM-1 downregulation and T cell exhaustion in tumors. Subclinical cholestasis defined by elevation of γ-glutamyl transferase (γGT) correlated with increased TCDCA and decreased soluble MAdCAM-1 in plasma and predicted poor survival in multivariate analyses in six cohorts of patients who received immunotherapy. Hence, subclinical cholestasis accompanies gut dysbiosis, paving the way to immunoresistance. - Source: PubMed
Publication date: 2026/07/29
Mallard de La Varende Anne-LaureTian Ai-LingThomas SimonLahmar ImranMessaoudene MeriemLi SijingMotiño OmarGuillaume-Dit-Taunière HortenseIebba ValerioHurtado YoanPham Thao-NguyenThélémaque CassandraAraujo-Voces MiguelSuissa DeborahLy PierreReich EllaVitali GiacomoArlunno Bryan ThierryDurand SylvereAprahamian FannyLeduc MarionForveille SabrinaKepp Oliverde la Calle-Fabregat CarlosSchippers AngelaWagner NorbertFournier Pierre-EdouardHonda KenyaMarmorino FedericaCremolini ChiaraMaleki Vareki SamanLenehan John GMarabelle AurélienDanlos François-XavierDeligne MargauxTruntzer CarolineGhiringhelli FrançoisRee Anne HBousquet Paula AMeltzer SebastianGinhoux FlorentRummel DeklanFu YousiQuinn Robert AAlves Costa Silva CarolinaIacovelli RobertoCiccarese ChiaraPorcari SerenaElkrief ArielleRouty BertrandIaniro GianlucaDerosa LisaKroemer GuidoFidelle MarineZitvogel Laurence - The substantial biological heterogeneity of thyroid cancer, particularly within follicular-patterned lesions, underscores the need for improved molecular tools for risk stratification. Genetic variability in the pathways regulating cell adhesion, immune interactions, and extracellular matrix remodeling may influence tumor behavior and the complexity of diagnosis. In this study, we conducted integrated and genetic analyses to evaluate the role of polymorphisms in genes encoding immunoglobulin superfamily adhesion molecules, integrins, junctional proteins, matrix metalloproteinases, and extracellular matrix-associated proteins. Using multiple bioinformatics platforms, we screened 407,812 polymorphisms across 22 candidate genes and prioritized 133 variants with high predicted functional impact. Eight selected single-nucleotide polymorphisms were genotyped in a cohort of 648 individuals, including patients with benign thyroid nodules (n = 152), malignant thyroid nodules (n = 171), and healthy controls (n = 325). Clinical validation revealed that rs3745925 significantly distinguished follicular adenoma from controls (p = 0.017, OR: 3.15; 95% CI: 1.63-6.05), goiter (p = 0.019, OR: 3.18; 95% CI: 1.49-6.85), and papillary thyroid carcinoma (p = 0.009, OR: 3.49; 95% CI: 1.73-7.09). This association remained robust after Bonferroni correction, underscoring its potential as a priority candidate. Additionally, rs1143683, rs2230433, and rs5498 were associated with tumor multifocality (p = 0.0428, p = 0.0008, and p < 0.0001, respectively). These findings demonstrate the feasibility of integrating bioinformatics-driven variant prioritization with clinical validation methods. Among the evaluated polymorphisms, rs3745925 emerged as a promising auxiliary biomarker warranting further evaluation for the characterization of follicular-patterned thyroid lesions. - Source: PubMed
Publication date: 2026/06/23
Rabi Larissa TeodoroPeres Karina ColomberaTeixeira Elisangela De SouzaTincani Alfio JoséBufalo Natassia ElenaWard Laura Sterian