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UID:DSC-21345
DTSTART;TZID=Europe/Berlin:20241023T100000
SEQUENCE:1729661837
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URL:https://www.dresden-science-calendar.de/calendar/de/detail/21345
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: Galleria)\n  Street: Pfot
 enhauerstraße 108\n  City: 01307 Dresden\n  Phone: +49 351 210-0\n  Fax: 
 +49 351 210-2000\nDescription: Macrophages are the earliest set of immune 
 cells that populate the murine skin. However\, much less is understood abo
 ut their role in regulating developmental and inflammatory programs in the
  developing skin. Our study suggests that macrophages in the developing sk
 in can respond to sterile inflammatory cues by augmenting the synthesis of
  ECM (extracellular matrix) remodeling enzymes called MMPs (matrix metallo
 proteinases). These MMPs exacerbate chronic inflammation by generating DAM
 Ps (damage-associated molecular patterns). We further show that this funct
 ional state of the macrophages is partly directed by the metabolite lactat
 e that is generated by the epithelial compartment of the skin in condition
 s of sterile inflammation. Remarkably\, inhibition of the lactate-mediated
  metabolic crosstalk between the skin epithelia and macrophages leads to a
  substantial reduction in the macrophage effector function and\, in turn\,
  inflammation. We further show that the principle of lactate metabolic cro
 sstalk can be targeted to treat inflammation in the imiquimod-induced mice
  model of psoriasis. Finally\, using a macrophage-depleted mouse model sys
 tem we investigate the role of these cell types in regulating skin develop
 ment. Our results suggest that macrophage-mediated remodeling of the skin 
 ECM is essential for driving the development of skin appendages. These stu
 dies have elucidated the developmental and inflammatory roles of macrophag
 es in the developing skin.  Publications and Patent:  1. Ayyangar U\, Kark
 hanis A\, Tay H\, Afandi AFB\, Bhattacharjee O\, KS L\, Lee SH\, Chan J &a
 mp\; Raghavan S (2024) Metabolic rewiring of macrophages by epidermal-deri
 ved lactate promotes sterile inflammation in the murine skin. EMBO J  2. B
 hattacharjee O\, Ayyangar U\, Kurbet AS\, Lakshmanan V\, Palakodeti D\, Gi
 nhoux F &amp\; Raghavan S (2021) Epithelial-Macrophage Crosstalk Initiates
  Sterile Inflammation in Embryonic Skin. Front Immunol 12.  3. Bhattacharj
 ee O\, Ayyangar U\, Kurbet AS\, Ashok D &amp\; Raghavan S (2019) Unravelin
 g the ECM-immune cell crosstalk in skin diseases. Front Cell Dev Biol 7 do
 i:10.3389/fcell.2019.00068.  4. [Patent] Citric Acid Cycle and Lactate Tra
 nsport Inhibitors for Prevention and/or Treatment of Skin Disorders PCT Ap
 plication number: PCT/IB2022/061996 Date of Filing: 10.12.2022 Inventors: 
 Uttkarsh Ayyangar\, Srikala Raghavan.
DTSTAMP:20260818T104242Z
CREATED:20241010T054117Z
LAST-MODIFIED:20241023T053717Z
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