CD300b regulates intestinal inflammation and promotes repair in colitis.

Chronic inflammation is a hallmark charataristic of various inflammatory diseases including inflammatory bowel disease. Subsequently, current therapeutic approaches target immune-mediated pathways as means for therapeutic intervention and promotion of mucosal healing and repair. Emerging data demonstrate important roles for CD300 receptor family members in settings of innate immunity as well as in allergic and autoimmune diseases.

Metastasis-Entrained Eosinophils Enhance Lymphocyte-Mediated Antitumor Immunity.

The recognition of the immune system as a key component of the tumor microenvironment (TME) led to promising therapeutics. Because such therapies benefit only subsets of patients, understanding the activities of immune cells in the TME is required. Eosinophils are an integral part of the TME especially in mucosal tumors.

In Vitro Evaluation of the Activity of Terpenes and Cannabidiol against Human Coronavirus E229.

The activity of a new, terpene-based formulation, code-named NT-VRL-1, against Human Coronavirus (HCoV) strain 229E was evaluated in human lung fibroblasts (MRC-5 cells), with and without the addition of cannabidiol (CBD). The main constituents in the terpene formulation used for the experiment were beta caryophyllene, eucalyptol, and citral. The tested formulation exhibited an antiviral effect when it was pre-incubated with the host cells prior to virus infection.

A key role for IL-13 signaling via the type 2 IL-4 receptor in experimental atopic dermatitis.

IL-13 and IL-4 are potent mediators of type 2-associated inflammation such as those found in atopic dermatitis (AD). IL-4 shares overlapping biological functions with IL-13, a finding that is mainly explained by their ability to signal via the type 2 IL-4 receptor (R), which is composed of IL-4Rα in association with IL-13Rα1. Nonetheless, the role of the type 2 IL-4R in AD remains to be clearly defined.

Activated Eosinophils Exert Antitumorigenic Activities in Colorectal Cancer.

Immunotherapies targeting T lymphocytes are revolutionizing cancer therapy but only benefit a subset of patients, especially in colorectal cancer. Thus, additional insight into the tumor microenvironment (TME) is required. Eosinophils are bone marrow-derived cells that have been largely studied in the context of allergic diseases and parasite infections.

Eosinophils support adipocyte maturation and promote glucose tolerance in obesity.

Accumulating data have indicated a fundamental role of eosinophils in regulating adipose tissue homeostasis. Here, we performed whole-genome RNA sequencing of the small intestinal tract, which suggested the presence of impaired lipid metabolism in eosinophil-deficient ΔdblGATA mice. ΔdblGATA mice fed a high-fat diet (HFD) showed reduced body fat mass, impaired enlargement of adipocytes, decreased expression of adipogenic genes, and developed glucose intolerance.

Cooperation between Hsp90 and mortalin/GRP75 in resistance to cell death induced by complement C5b-9.

Cancer cells are commonly more resistant to cell death activated by the membranolytic protein complex C5b-9. Several surface-expressed and intracellular proteins that protect cells from complement-dependent cytotoxicity (CDC) have been identified. In this study, we investigated the function of heat shock protein 90 (Hsp90), an essential and ubiquitously expressed chaperone, overexpressed in cancer cells, in C5b-9-induced cell death.

CD300 family receptors regulate eosinophil survival, chemotaxis, and effector functions.

The CD300 family of receptors is an evolutionary conserved receptor family that belongs to the Ig superfamily and is expressed predominantly by the myeloid lineage. Over the past couple of years, accumulating data have shown that eosinophils express various Ig superfamily receptors that regulate key checkpoints in their biology including their maturation, transition from the bone marrow to the peripheral blood, migration, adhesion, survival, and effector functions in response to numerous activating signals such as IL-4, IL-33, and bacteria. In this review, we will present the emerging roles of CD300 family receptors and specifically CD300a and CD300f in the regulation of these eosinophil activities.

Mouse Eosinophils: Identification, Isolation, and Functional Analysis.

Eosinophils are bone marrow-derived cells that differentiate in the bone marrow and migrate into the peripheral blood primarily under the regulation of interleukin (IL)-5. Eosinophil levels in the blood are relatively low. However, under steady-state conditions and in settings of allergic inflammation, parasite infections, or even cancer, they migrate and mainly reside in mucosal tissues where they have key effector and immune-modulating functions.

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

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 /Cd300f mice revealed marked and distinct increases in eosinophil levels and their production of IL-4 in the white and brown adipose tissues.

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

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.

Elevated levels of mitochondrial mortalin and cytosolic HSP70 in blood as risk factors in patients with colorectal cancer.

Mortalin/GRP75 is a ubiquitous mitochondrial chaperone related to the cytosolic heat shock protein 70 (HSP70). It protects cells from senescence and apoptosis and is overexpressed in cancer cells. Cell resistance to complement-dependent cytotoxicity depends on mortalin and during complement attack mortalin is released from cells.

Mechanisms regulating the secretion of the promalignancy chemokine CCL5 by breast tumor cells: CCL5's 40s loop and intracellular glycosaminoglycans.

The chemokine CCL5 (RANTES) plays active promalignancy roles in breast malignancy. The secretion of CCL5 by breast tumor cells is an important step in its tumor-promoting activities; therefore, inhibition of CCL5 secretion may have antitumorigenic effects. We demonstrate that, in breast tumor cells, CCL5 secretion necessitated the trafficking of CCL5-containing vesicles on microtubules from the endoplasmic reticulum (ER) to the post-Golgi stage, and CCL5 release was regulated by the rigidity of the actin cytoskeleton.