Lysophosphatidic Acid-Mediated GPR35 Signaling in CX3CR1+ Macrophages Regulates Intestinal Homeostasis - UNICANCER Access content directly
Journal Articles Cell Reports Year : 2020

Lysophosphatidic Acid-Mediated GPR35 Signaling in CX3CR1+ Macrophages Regulates Intestinal Homeostasis

Berna Kaya
  • Function : Author
Cristian Doñas
  • Function : Author
Philipp Wuggenig
  • Function : Author
Oscar E Diaz
  • Function : Author
Rodrigo A Morales
  • Function : Author
Hassan Melhem
  • Function : Author
Tanay Kaymak
  • Function : Author
Srustidhar Das
  • Function : Author
Petr Hruz
  • Function : Author
Yannick Franc
  • Function : Author
Florian Geier
  • Function : Author
C. Korcan Ayata
  • Function : Author
Eduardo J Villablanca
Jan Hendrik Niess
  • Function : Author

Abstract

Single-nucleotide polymorphisms in the gene encoding G protein-coupled receptor 35 (GPR35) are associated with increased risk of inflammatory bowel disease. However, the mechanisms by which GPR35 modulates intestinal immune homeostasis remain undefined. Here, integrating zebrafish and mouse experimental models, we demonstrate that intestinal Gpr35 expression is microbiota dependent and enhanced upon inflammation. Moreover, murine GPR35+ colonic macrophages are characterized by enhanced production of pro-inflammatory cytokines. We identify lysophosphatidic acid (LPA) as a potential endogenous ligand produced during intestinal inflammation, acting through GPR35 to induce tumor necrosis factor (Tnf) expression in macrophages. Mice lacking Gpr35 in CX3CR1+ macrophages aggravate colitis when exposed to dextran sodium sulfate, which is associated with decreased transcript levels of the corticosterone-generating gene Cyp11b1 and macrophage-derived Tnf. Administration of TNF in these mice restores Cyp11b1 expression and intestinal corticosterone production and ameliorates DSS-induced colitis. Our findings indicate that LPA signals through GPR35 in CX3CR1+ macrophages to maintain TNF-mediated intestinal homeostasis.

Domains

Innate immunity
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Dates and versions

hal-03968569 , version 1 (01-02-2023)

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Berna Kaya, Cristian Doñas, Philipp Wuggenig, Oscar E Diaz, Rodrigo A Morales, et al.. Lysophosphatidic Acid-Mediated GPR35 Signaling in CX3CR1+ Macrophages Regulates Intestinal Homeostasis. Cell Reports, 2020, 32 (5), pp.107979. ⟨10.1016/j.celrep.2020.107979⟩. ⟨hal-03968569⟩
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