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CD300f:IL-5 cross-talk inhibits adipose tissue eosinophil homing and subsequent IL-4 production.


ABSTRACT: Eosinophils and their associated cytokines IL-4 and IL-5 are emerging as central orchestrators of the immune-metabolic axis. Herein, we demonstrate that cross-talk between the Ig-superfamily receptor CD300f and IL-5 is a key checkpoint that modifies the ability of eosinophils to regulate metabolic outcomes. Generation of Il5 Tg /Cd300f -/- mice revealed marked and distinct increases in eosinophil levels and their production of IL-4 in the white and brown adipose tissues. Consequently, Il5 Tg /Cd300f -/- mice had increased alternatively activated macrophage accumulation in the adipose tissue. Cd300f -/- mice displayed age-related accumulation of eosinophils and macrophages in the adipose tissue and decreased adipose tissue weight, which was associated with decreased diet-induced weight gain and insulin resistance. Notably, Il5 Tg /CD300f -/- were protected from diet-induced weight gain and glucose intolerance. These findings highlight the cross-talk between IL-5 receptor and CD300f as a novel pathway regulating adipose tissue eosinophils and offer new entry points for therapeutic intervention for obesity and its complications.

SUBMITTER: Rozenberg P 

PROVIDER: S-EPMC5517555 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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CD300f:IL-5 cross-talk inhibits adipose tissue eosinophil homing and subsequent IL-4 production.

Rozenberg Perri P   Reichman Hadar H   Zab-Bar Israel I   Itan Michal M   Pasmanik-Chor Metsada M   Bouffi Carine C   Qimron Udi U   Bachelet Ido I   Fulkerson Patricia C PC   Rothenberg Marc E ME   Munitz Ariel A  

Scientific reports 20170719 1


Eosinophils and their associated cytokines IL-4 and IL-5 are emerging as central orchestrators of the immune-metabolic axis. Herein, we demonstrate that cross-talk between the Ig-superfamily receptor CD300f and IL-5 is a key checkpoint that modifies the ability of eosinophils to regulate metabolic outcomes. Generation of Il5 <sup>Tg</sup> /Cd300f <sup>-/-</sup> mice revealed marked and distinct increases in eosinophil levels and their production of IL-4 in the white and brown adipose tissues. Co  ...[more]

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