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UID:DSC-21448
DTSTART;TZID=Europe/Berlin:20241111T110000
SEQUENCE:1731221314
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URL:https://www.dresden-science-calendar.de/calendar/de/detail/21448
LOCATION:MPI-CBG\, Pfotenhauerstraße 10801307 Dresden
SUMMARY:Ayyangar: Unraveling Epithelial - Immune Crosstalk in Murine Skin D
 evelopment and Disease
CLASS:PUBLIC
DESCRIPTION:Speaker: Uttkarsh Ayyangar\nInstitute of Speaker: Institute of 
 Stem Cell Science and Regenerative Medicine (InStem)\, Bengaluru\, India\n
 Topics:\n\n Location:\n  Name: MPI-CBG (MPI-CBG CBG Galleria)\n  Street: P
 fotenhauerstraße 108\n  City: 01307 Dresden\n  Phone: +49 351 210-0\n  Fa
 x: +49 351 210-2000\nDescription: Macrophages are the earliest set of immu
 ne cells that populate the murine skin. However\, much less is understood 
 about their role in regula\;ng developmental and inflammatory programs in 
 the developing skin. Our study suggests that macrophages in the developing
  skin can respond to sterile inflammatory cues by augmen\;ng the synthesis
  of ECM (extracellular matrix) remodeling enzymes called MMPs (matrix meta
 lloproteinases). These MMPs exacerbate chronic inflamma\;on by genera\;ng 
 DAMPs (damage-associated molecular paJerns). We further show that this fun
 c\;onal state of the macrophages is partly directed by the metabolite lact
 ate that is generated by the epithelial compartment of the skin in condi\;
 ons of sterile inflamma\;on. Remarkably\, inhibi\;on of the lactate-mediat
 ed metabolic crosstalk between the skin epithelia and macrophages leads to
  a substan\;al reduc\;on in the macrophage effector func\;on and\, in turn
 \, inflamma\;on. We further show that the principle of lactate metabolic c
 rosstalk can be targeted to treat inflamma\;on in the imiquimod-induced mi
 ce model of psoriasis. Finally\, using a macrophage-depleted mouse model s
 ystem we inves\;gate the role of these cell types in regula\;ng skin devel
 opment. Our results suggest that macrophage-mediated remodeling of the ski
 n ECM is essen\;al for driving the development of skin appendages. These s
 tudies have elucidated the developmental and inflammatory roles of macroph
 ages in the developing skin. Publica\;ons and Patent: 1. Ayyangar U\, Kark
 hanis A\, Tay H\, Afandi AFB\, BhaJacharjee O\, KS L\, Lee SH\, Chan J &am
 p\; Raghavan S (2024) Metabolic rewiring of macrophages by epidermal-deriv
 ed lactate promotes sterile inflamma\;on in the murine skin. EMBO J 2. Bha
 Jacharjee O\, Ayyangar U\, Kurbet AS\, Lakshmanan V\, Palakode\; D\, Ginho
 ux F &amp\; Raghavan S (2021) Epithelial-Macrophage Crosstalk Ini\;ates St
 erile Inflamma\;on in Embryonic Skin. Front Immunol 12. 3. BhaJacharjee O\
 , Ayyangar U\, Kurbet AS\, Ashok D &amp\; Raghavan S (2019) Unraveling the
  ECM-immune cell crosstalk in skin diseases. Front Cell Dev Biol 7 doi:10.
 3389/fcell.2019.00068. 4. [Patent] Citric Acid Cycle and Lactate Transport
  Inhibitors for Preven\;on and/or Treatment of Skin Disorders PCT Applica\
 ;on number: PCT/IB2022/061996 Date of Filing: 10.12.2022 Inventors: UJkars
 h Ayyangar\, Srikala Raghavan.
DTSTAMP:20260707T001858Z
CREATED:20241105T063939Z
LAST-MODIFIED:20241110T064834Z
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