Gpr137b is an orphan G-protein-coupled receptor associated with M2 macrophage polarization.

Macrophages are classified mainly into two subtypes, M1 and M2, which exhibit distinct phenotypes, based on their microenvironment. Although recent studies have suggested that G-protein-coupled receptors (GPCRs) are associated with M1/M2 macrophage polarization, available information on GPCR-mediated macrophage polarization is still limited. In the present study, we identified Gpr137b as an orphan GPCR abundantly expressed in RAW264, a mouse macrophage cell line, and illuminated its role in M2 macrophage polarization. We generated Gpr137b-knockout (Gpr137b-KO) clones of RAW264 cells using the CRISPR/Cas9 genome editing system. Two independent Gpr137b-KO clones were isolated, which were demonstrated to have frameshifting 188-nucleotide deletions at a region containing the ATG start codon of Gpr137b. Consistently, qRT-PCR analysis revealed that the deleted region is not transcribed. We then treated the Gpr137b-KO and wildtype RAW264 cells with interleukin-4 (IL-4) to induce M2 macrophage polarization. Microarray analysis revealed that the IL-4-induced gene expression of representative M2 macrophage markers was significantly reduced in the Gpr137b-KO cells, and this was validated by qRT-PCR analysis. By contrast, M1 macrophage marker gene expression induced by lipopolysaccharide was unaffected by Gpr137b-KO. Collectively, the current study shows that Gpr137b is a possible regulator of M2 macrophage polarization.

MATRIN3 deficiency triggers autoinflammation via cGAS-STING activation.

Interferon-stimulated genes (ISGs) comprise a program of immune effectors important for host immune defense. When uncontrolled, ISGs play a central role in interferonopathies and other inflammatory diseases. The mechanisms responsible for turning on ISGs are not completely known. By investigating MATRIN3 (MATR3), a nuclear RNA-binding protein mutated in familial ALS, we found that perturbing MATR3 results in elevated expression of ISGs. Using an integrative approach, we elucidate a pathway that leads to activation of cGAS-STING. This outlines a plausible mechanism for pathogenesis in a subset of ALS, and suggests new diagnostic and therapeutic approaches for this fatal disease.

Regulation of Macrophage Polarization in Allergy by Noncoding RNAs.

Allergy is a type 2 immune reaction triggered by antigens known as allergens, including food and environmental substances such as peanuts, plant pollen, fungal spores, and the feces and debris of mites and insects. Macrophages are myeloid immune cells with phagocytic abilities that process exogenous and endogenous antigens. Upon activation, they can produce effector molecules such as cytokines as well as anti-inflammatory molecules. The dysregulation of macrophage function can lead to excessive type 1 inflammation as well as type 2 inflammation, which includes allergic reactions. Thus, it is important to better understand how macrophages are regulated in the pathogenesis of allergies. Emerging evidence highlights the role of noncoding RNAs (ncRNAs) in macrophage polarization, which in turn can modify the pathogenesis of various immune-mediated diseases, including allergies. This review summarizes the current knowledge regarding this topic and considers three classes of ncRNAs: microRNAs, long ncRNAs, and circular ncRNAs. Understanding the roles of these ncRNAs in macrophage polarization will provide new insights into the pathogenesis of allergies and identify potential novel therapeutic targets.

Datasets of microarray analysis to identify Gpr137b-dependent interleukin-4-responsive genes in the mouse macrophage cell line RAW264.

Macrophages are classified mainly into two subtypes, M1 and M2, which exhibit distinct phenotypes, based on their microenvironment. We have recently demonstrated that Gpr137b is abundantly expressed in RAW264 macrophages, "Gpr137b is an orphan G-protein-coupled receptor associated with M2 macrophage polarization" (Islam et al., in press) [1]. Although recent studies have suggested that G-protein-coupled receptors (GPCRs) are associated with M1/M2 macrophage polarization ("G-protein-coupled bile acid receptor 1 (GPBAR1, TGR5) agonists reduce the production of proinflammatory cytokines and stabilize the alternative macrophage phenotype" (Hogenauer et al., 2014) [2], "Leukotriene B4 promotes neovascularization and macrophage recruitment in murine wet-type AMD models" (Sasaki et al., 2018) [3]), available information about GPCR-mediated macrophage polarization is still limited. This prompted us to generate Gpr137b-knockout (KO) RAW264 clones using the CRISPR/Cas9 genome editing system to elucidate the function of Gpr137b in interleukin (IL)-4-induced M2 macrophage polarization (Islam et al., in press) [1]. Here we present the datasets of a microarray analysis to identify Gpr137b-dependent IL-4-responsive genes in RAW264 cells. The raw microarray data are available in the Gene Expression Omnibus database (https://www.ncbi.nlm.nih.gov/geo/) under the accession number GSE117578, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE117578.