title: Adipose Recruitment and Activation of Plasmacytoid Dendritic Cells Fuel Metaflammation.
abstract: In obese individuals, visceral adipose tissue (VAT) is the seat of chronic low-grade inflammation (metaflammation), but the mechanistic link between increased adiposity and metaflammation largely remains unclear. In obese individuals, deregulation of a specific adipokine, chemerin, contributes to innate initiation of metaflammation by recruiting circulating plasmacytoid dendritic cells (pDCs) into VAT through chemokine-like receptor 1 (CMKLR1). Adipose tissue-derived high-mobility group B1 (HMGB1) protein activates Toll-like receptor 9 (TLR9) in the adipose-recruited pDCs by transporting extracellular DNA through receptor for advanced glycation end products (RAGE) and induces production of type I interferons (IFNs). Type I IFNs in turn help in proinflammatory polarization of adipose-resident macrophages. IFN signature gene expression in VAT correlates with both adipose tissue and systemic insulin resistance (IR) in obese individuals, which is represented by ADIPO-IR and HOMA2-IR, respectively, and defines two subgroups with different susceptibility to IR. Thus, this study reveals a pathway that drives adipose tissue inflammation and consequent IR in obesity.
authors: Division of Cancer Biology and Inflammatory Disorders, Council of Scientific and Industrial Research-Indian Institute of Chemical Biology, Kolkata, India.
authors: Amrit Raj
authors: AR
authors: Ghosh
authors: Division of Cancer Biology and Inflammatory Disorders, Council of Scientific and Industrial Research-Indian Institute of Chemical Biology, Kolkata, India.
authors: Roopkatha
authors: R
authors: Bhattacharya
authors: Division of Cancer Biology and Inflammatory Disorders, Council of Scientific and Industrial Research-Indian Institute of Chemical Biology, Kolkata, India.
authors: Shamik
authors: S
authors: Bhattacharya
authors: Division of Cell Biology and Physiology, Council of Scientific and Industrial Research-Indian Institute of Chemical Biology, Kolkata, India.
authors: Titli
authors: T
authors: Nargis
authors: Division of Cancer Biology and Inflammatory Disorders, Council of Scientific and Industrial Research-Indian Institute of Chemical Biology, Kolkata, India.
authors: Oindrila
authors: O
authors: Rahaman
authors: Division of Cancer Biology and Inflammatory Disorders, Council of Scientific and Industrial Research-Indian Institute of Chemical Biology, Kolkata, India.
authors: Pritam
authors: P
authors: Duttagupta
authors: Division of Cancer Biology and Inflammatory Disorders, Council of Scientific and Industrial Research-Indian Institute of Chemical Biology, Kolkata, India.
authors: Deblina
authors: D
authors: Raychaudhuri
authors: Division of Cancer Biology and Inflammatory Disorders, Council of Scientific and Industrial Research-Indian Institute of Chemical Biology, Kolkata, India.
authors: Chinky Shiu Chen
authors: CS
authors: Liu
authors: Division of Cancer Biology and Inflammatory Disorders, Council of Scientific and Industrial Research-Indian Institute of Chemical Biology, Kolkata, India.
authors: Shounak
authors: S
authors: Roy
authors: Department of Rheumatology, Institute of Postgraduate Medical Education and Research, Kolkata, India.
authors: Parasar
authors: P
authors: Ghosh
authors: ILS Hospitals, Kolkata, India.
authors: Shashi
authors: S
authors: Khanna
authors: ILS Hospitals, Kolkata, India.
authors: Tamonas
authors: T
authors: Chaudhuri
authors: ILS Hospitals, Kolkata, India.
authors: Om
authors: O
authors: Tantia
authors: Zentrum Allergie und Umwelt, Technical University of Munich and Helmholtz Centre Munich, Munich, Germany.
authors: Stefan
authors: S
authors: Haak
authors: Division of Cancer Biology and Inflammatory Disorders, Council of Scientific and Industrial Research-Indian Institute of Chemical Biology, Kolkata, India.
authors: Santu
authors: S
authors: Bandyopadhyay
authors: Department of Endocrinology, Institute of Postgraduate Medical Education and Research, Kolkata, India.
authors: Satinath
authors: S
authors: Mukhopadhyay
authors: Division of Cell Biology and Physiology, Council of Scientific and Industrial Research-Indian Institute of Chemical Biology, Kolkata, India.
authors: Partha
authors: P
authors: Chakrabarti
authors: Division of Cancer Biology and Inflammatory Disorders, Council of Scientific and Industrial Research-Indian Institute of Chemical Biology, Kolkata, India dipyaman@iicb.res.in.
authors: Dipyaman
authors: http://orcid.org/0000-0002-7786-1795
authors: D
authors: Ganguly
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003713:Dendritic Cells / Q000378:metabolism*; D005260:Female; D017127:Glycation End Products, Advanced / Q000378:metabolism; D024243:HMGB1 Protein / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D007333:Insulin Resistance / Q000235:genetics / Q000502:physiology; D007370:Interferon Type I / Q000235:genetics / Q000378:metabolism; D050152:Intra-Abdominal Fat / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D019707:Receptors, Chemokine; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism; D051217:Toll-Like Receptor 9 / Q000235:genetics / Q000378:metabolism*
chemical_list: C486456:CMKLR1 protein, mouse; D017127:Glycation End Products, Advanced; D024243:HMGB1 Protein; D007370:Interferon Type I; D019707:Receptors, Chemokine; D043562:Receptors, G-Protein-Coupled; D051217:Toll-Like Receptor 9