2018
DOI: 10.1016/j.immuni.2018.04.021
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TRPV4 Channel Signaling in Macrophages Promotes Gastrointestinal Motility via Direct Effects on Smooth Muscle Cells

Abstract: Intestinal macrophages are critical for gastrointestinal (GI) homeostasis, but our understanding of their role in regulating intestinal motility is incomplete. Here, we report that CX3C chemokine receptor 1-expressing muscularis macrophages (MMs) were required to maintain normal GI motility. MMs expressed the transient receptor potential vanilloid 4 (TRPV4) channel, which senses thermal, mechanical, and chemical cues. Selective pharmacologic inhibition of TRPV4 or conditional deletion of TRPV4 from macrophages… Show more

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Cited by 64 publications
(69 citation statements)
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References 80 publications
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“…As TRPV4 has been implicated in alveolar and intestinal macrophages (Hamanaka et al, 2010; Luo et al, 2018; Pairet et al, 2018), sensing of mechanical tissue deformation may constitute a conserved role of tissue resident macrophages throughout the body. The ability to directly interact with parenchymal cells and sensing mechanical inputs may reflect an additional division of labor between tissue resident and infiltrating monocyte-derived macrophages.…”
Section: Discussionmentioning
confidence: 99%
“…As TRPV4 has been implicated in alveolar and intestinal macrophages (Hamanaka et al, 2010; Luo et al, 2018; Pairet et al, 2018), sensing of mechanical tissue deformation may constitute a conserved role of tissue resident macrophages throughout the body. The ability to directly interact with parenchymal cells and sensing mechanical inputs may reflect an additional division of labor between tissue resident and infiltrating monocyte-derived macrophages.…”
Section: Discussionmentioning
confidence: 99%
“…Infiltrating inflammatory cells have been shown to be in close proximity to SMC in the muscular layers and directly affect smooth muscle function by releasing pro‐inflammatory cytokines . In rats, POI decreased jejunal and colonic circular smooth contractions which are associated with decreased gastrointestinal transit linked to increasing pro‐inflammatory cytokines .…”
Section: Discussionmentioning
confidence: 99%
“…This enzyme is a key component of O 2 ‐dependent microbial activity of phagocytes that, in turn, induces muscular macrophages and polymorphonuclear neutrophil infiltration, resulting in the production of high levels of pro‐inflammatory cytokines such as tumor necrosis factor‐α (TNF‐α) and interleukin‐6 (IL‐6) . Infiltrating inflammatory cells have been shown to be in close proximity to SMC in the muscularis layers and directly affect smooth muscle function by releasing pro‐inflammatory cytokines …”
Section: Introductionmentioning
confidence: 99%
“…In addition to their interaction with neurons, it was recently demonstrated that muscularis macrophages can directly interact with smooth muscle cells via TRPV4-mediated release of prostaglandin E2, affecting colonic motility. 82 Indeed, Trpv4-floxed mice showed significant reduction in colonic contraction upon treatment with GSK101, a TRPV4 channel agonist, an effect which was independent from neuronal input. These findings highlight that muscularis macrophages can also directly influence smooth muscle cells without input from the ENS.…”
Section: Muscularis Macrophagesmentioning
confidence: 98%