Interleukin‐33 requires <scp>CMRF</scp>35‐like molecule‐1 expression for induction of myeloid cell activation

Shik, Dana; Moshkovits, Itay; Karo‐Atar, Danielle; Reichman, Hadar; Munitz, Ariel

doi:10.1111/all.12388

Cited by 24 publications

(29 citation statements)

References 49 publications

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“…These data are consistent with our finding that IL-4 increased the expression of CD300f in macrophages and that IL-33 induced the expression of CD300f in eosinophils (21). Of note, activation of macrophages with IL-13 did not increase the expression of CD300f.…”

Section: Cd300f Is Up-regulated In Monocytes and Eosinophils Obtainedsupporting

confidence: 93%

CD300f associates with IL-4 receptor α and amplifies IL-4–induced immune cell responses

Moshkovits

Karo‐Atar

Itan

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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IL-4 receptor (R) α, the common receptor chain for IL-4 and IL-13, is a critical component in IL-4-and IL-13-mediated signaling and subsequent effector functions such as those observed in type 2 inflammatory responses. Nonetheless, the existence of intrinsic pathways capable of amplifying IL-4Rα-induced responses remains unknown. In this study, we identified the myeloid-associated Ig receptor CD300f as an IL-4-induced molecule in macrophages. Subsequent analyses demonstrated that CD300f was colocalized and physically associated with IL-4Rα. Using Cd300f −/− cells and receptor cross-linking experiments, we established that CD300f amplified IL-4Rα-induced responses by augmenting IL-4/IL-13-induced signaling, mediator release, and priming. Consistently, IL-4-and aeroallergen-treated Cd300f −/− mice displayed decreased IgE production, chemokine expression, and inflammatory cell recruitment. Impaired responses in Cd300f−/− mice were not due to the inability to generate a proper Th2 response, because IL-4/IL-13 levels were markedly increased in allergen-challenged Cd300f −/− mice, a finding that is consistent with decreased cytokine consumption. Finally, CD300f expression was increased in monocytes and eosinophils obtained from allergic rhinitis patients. Collectively, our data highlight a previously unidentified role for CD300f in IL-4Rα-induced immune cell responses. These data provide new insights into the molecular mechanisms governing IL-4Rα-induced responses, and may provide new therapeutic tools to target IL-4 in allergy and asthma.IL-4 receptor | eosinophil | macrophage | CD300f | inflammation

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Section: Cd300f Is Up-regulated In Monocytes and Eosinophils Obtainedsupporting

confidence: 93%

CD300f associates with IL-4 receptor α and amplifies IL-4–induced immune cell responses

Moshkovits

Karo‐Atar

Itan

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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“…3D). Thereafter, I.29 cells were stimulated with IL-5 and phosphorylation of ERK was determined using PhosphoFlow as we previously published 29–32 . IL-5 stimulated I.29 cells containing an empty vector displayed elevated ERK phosphorylation (Fig.…”

Section: Resultsmentioning

confidence: 99%

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

Rozenberg

Reichman

Zab-Bar

et al. 2017

Sci Rep

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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.

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“…In vitro, IL-33, a cytokine that has a key role in initiating Th2 responses, upregulates the expression of CD300a and CD300f on eosinophils, and it only upregulates the expression of CD300a on bone marrow-derived mast cells. However, injection of IL-33 in the peritoneal cavity did not induce the expression of CD300a in any of the analyzed cell types in contrast to the IL-33-induced upregulation of CD300f in vivo (34). These results may explain the requirement of CD300f, but not CD300a, for IL-33-induced eosinophil and mast cell activation (34).…”

Section: Regulation Of Expressionmentioning

confidence: 86%

“…However, injection of IL-33 in the peritoneal cavity did not induce the expression of CD300a in any of the analyzed cell types in contrast to the IL-33-induced upregulation of CD300f in vivo (34). These results may explain the requirement of CD300f, but not CD300a, for IL-33-induced eosinophil and mast cell activation (34).…”

Section: Regulation Of Expressionmentioning

confidence: 86%

The Biology and Disease Relevance of CD300a, an Inhibitory Receptor for Phosphatidylserine and Phosphatidylethanolamine

Zenarruzabeitia

Vitallé

Eguizábal³

et al. 2015

The Journal of Immunology

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The CD300a inhibitory receptor belongs to the CD300 family of cell surface molecules that regulate a diverse array of immune cell processes. The inhibitory signal of CD300a depends on the phosphorylation of tyrosine residues embedded in ITIMs of the cytoplasmic tail. CD300a is broadly expressed on myeloid and lymphoid cells, and its expression is differentially regulated depending on the cell type. The finding that CD300a recognizes phosphatidylserine and phosphatidylethanolamine, two aminophospholipids exposed on the outer leaflet of dead and activated cells, has shed new light on its role in the modulation of immune functions and in its participation in the host response to several diseases states, such as infectious diseases, cancer, allergy, and chronic inflammatory diseases. This review summarizes the literature on CD300a expression, regulation, signaling pathways, and ligand interaction, as well as its role in fine tuning immune cell functions and its clinical relevance.

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Interleukin‐33 requires CMRF35‐like molecule‐1 expression for induction of myeloid cell activation

Cited by 24 publications

References 49 publications

CD300f associates with IL-4 receptor α and amplifies IL-4–induced immune cell responses

CD300f associates with IL-4 receptor α and amplifies IL-4–induced immune cell responses

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

The Biology and Disease Relevance of CD300a, an Inhibitory Receptor for Phosphatidylserine and Phosphatidylethanolamine

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