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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Neuro-immune Interactions Drive Tissue Programming in Intestinal Macrophages

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Author(s):
Gabanyi, Ilana [1, 2] ; Muller, Paul A. [1] ; Feighery, Linda [1] ; Oliveira, Thiago Y. [3] ; Costa-Pinto, Frederico A. [1, 2] ; Mucida, Daniel [1]
Total Authors: 6
Affiliation:
[1] Rockefeller Univ, Lab Mucosal Immunol, 1230 York Ave, New York, NY 10065 - USA
[2] Univ Sao Paulo, Sch Vet Med, Dept Pathol, Ave Prof Orlando Marques de Paiva 87, BR-05508270 Sao Paulo - Brazil
[3] Rockefeller Univ, Lab Mol Immunol, 1230 York Ave, New York, NY 10065 - USA
Total Affiliations: 3
Document type: Journal article
Source: Cell; v. 164, n. 3, p. 378-391, JAN 28 2016.
Web of Science Citations: 130
Abstract

Proper adaptation to environmental perturbations is essential for tissue homeostasis. In the intestine, diverse environmental cues can be sensed by immune cells, which must balance resistance to microorganisms with tolerance, avoiding excess tissue damage. By applying imaging and transcriptional profiling tools, we interrogated how distinct microenvironments in the gut regulate residentmacrophages. We discovered that macrophages exhibit a high degree of gene-expression specialization dependent on their proximity to the gut lumen. Lamina propria macrophages (LpMs) preferentially expressed a pro-inflammatory phenotype when compared to muscularis macrophages (MMs), which displayed a tissue-protective phenotype. Upon luminal bacterial infection, MMs further enhanced tissue-protective programs, and this was attributed to swift activation of extrinsic sympathetic neurons innervating the gut muscularis and norepinephrine signaling to beta 2 adrenergic receptors on MMs. Our results reveal unique intra-tissue macrophage specialization and identify neuro-immune communication between enteric neurons and macrophages that induces rapid tissue-protective responses to distal perturbations. (AU)