title: Rheb1 deletion in myeloid cells aggravates OVA-induced allergic inflammation in mice.
abstract: The small GTPase ras homolog enriched in brain (Rheb) is a downstream target of tuberous sclerosis complex 1/2 (TSC1/2) and an upstream activator of the mechanistic target of rapamycin complex 1 (mTORC1), the emerging essential modulator of M1/M2 balance in macrophages. However, the role and regulatory mechanisms of Rheb in macrophage polarization and allergic asthma are not known. In the present study, we utilized a mouse model with myeloid cell-specific deletion of the Rheb1 gene and an ovalbumin (OVA)-induced allergic asthma model to investigate the role of Rheb1 in allergic asthma and macrophage polarization. Increased activity of Rheb1 and mTORC1 was observed in myeloid cells of C57BL/6 mice with OVA-induced asthma. In an OVA-induced asthma model, Rheb1-KO mice demonstrated a more serious inflammatory response, more mucus production, enhanced airway hyper-responsiveness, and greater eosinophil numbers in bronchoalveolar lavage fluid (BALF). They also showed increased numbers of bone marrow macrophages and BALF myeloid cells, elevated M2 polarization and reduced M1 polarization of macrophages. Thus, we have established that Rheb1 is critical for the polarization of macrophages and inhibition of allergic asthma. Deletion of Rheb1 enhances M2 polarization but decreases M1 polarization in alveolar macrophages, leading to the aggravation of OVA-induced allergic asthma.
authors.affiliation: Department of Cell Biology, School of Basic Medical Science, Southern Medical University, Guangzhou, Guangdong, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Li
authors.affiliation: Department of Cell Biology, School of Basic Medical Science, Southern Medical University, Guangzhou, Guangdong, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Cell Biology, School of Basic Medical Science, Southern Medical University, Guangzhou, Guangdong, China.
authors.forename: Kang Yan
authors.initials: KY
authors.lastname: Liang
authors.affiliation: Department of Cell Biology, School of Basic Medical Science, Southern Medical University, Guangzhou, Guangdong, China.
authors.forename: Song
authors.initials: S
authors.lastname: Xu
authors.affiliation: Department of Cell Biology, School of Basic Medical Science, Southern Medical University, Guangzhou, Guangdong, China.
authors.forename: Xue Juan
authors.initials: XJ
authors.lastname: Zhou
authors.affiliation: Department of Cell Biology, School of Basic Medical Science, Southern Medical University, Guangzhou, Guangdong, China.
authors.forename: Kang
authors.initials: K
authors.lastname: Tan
authors.affiliation: Department of Cell Biology, School of Basic Medical Science, Southern Medical University, Guangzhou, Guangdong, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Lin
authors.affiliation: Department of Cell Biology, School of Basic Medical Science, Southern Medical University, Guangzhou, Guangdong, China.
authors.forename: Xiao Chun
authors.initials: XC
authors.lastname: Bai
authors.affiliation: Department of Cell Biology, School of Basic Medical Science, Southern Medical University, Guangzhou, Guangdong, China.
authors.forename: Cui Lan
authors.initials: CL
authors.lastname: Yang
mesh_terms: D000485:Allergens / Q000276:immunology; D000818:Animals; D001249:Asthma / Q000235:genetics / Q000276:immunology / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D004195:Disease Models, Animal; D017353:Gene Deletion; D006967:Hypersensitivity / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D008262:Macrophage Activation / Q000235:genetics / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D000076222:Mechanistic Target of Rapamycin Complex 1 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D022423:Myeloid Cells / Q000276:immunology* / Q000378:metabolism*; D010047:Ovalbumin / Q000276:immunology*; D011485:Protein Binding; D000076205:Ras Homolog Enriched in Brain Protein / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism
chemical_list: D000485:Allergens; D000076205:Ras Homolog Enriched in Brain Protein; C490213:Rheb protein, mouse; D010047:Ovalbumin; D000076222:Mechanistic Target of Rapamycin Complex 1