title: Regulator of calcineurin 1 (Rcan1) is required for the development of pulmonary eosinophilia in allergic inflammation in mice.
abstract: The presence of eosinophils in the lung is often regarded as a defining feature of asthma. On allergen stimulation, numbers of eosinophils and their progenitors are increased in both the bone marrow and lungs. Eosinophil progenitors provide an ongoing supply of mature eosinophils. Here, we report that deficiency in the regulator of calcineurin 1 gene (Rcan1) leads to a near-complete absence of eosinophilia in ovalbumin-induced allergic asthma in mice. In the absence of Rcan1, bone marrow cells produce significantly fewer eosinophils in vivo and in vitro on interleukin-5 stimulation. Importantly, eosinophil progenitor populations are significantly reduced in both naïve and ovalbumin-challenged Rcan1(-/-) mice. Bone marrow cells from Rcan1(-/-) mice are capable of developing into fully mature eosinophils, suggesting that Rcan1 is required for eosinophil progenitor production but may not be necessary for eosinophil maturation. Thus, Rcan1 represents a novel contributor in the development of eosinophilia in allergic asthma through regulation of eosinophil progenitor production.
authors: Institute of Zoonosis, College of Animal Sciences and Veterinary Medicine, Jilin University, Changchun, China.
authors: Yong Jun
authors: YJ
authors: Yang
authors: Adam J
authors: AJ
authors: Macneil
authors: Robert
authors: R
authors: Junkins
authors: Svetlana O
authors: SO
authors: Carrigan
authors: Jin-Tian
authors: JT
authors: Tang
authors: Nicholas
authors: N
authors: Forward
authors: David
authors: D
authors: Hoskin
authors: Jason N
authors: JN
authors: Berman
authors: Tong-Jun
authors: TJ
authors: Lin
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001249:Asthma / Q000209:etiology* / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D019703:Calcineurin / Q000378:metabolism; D002135:Calcium-Binding Proteins; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004804:Eosinophils / Q000473:pathology; D006412:Hematopoietic Stem Cells / Q000473:pathology; D015847:Interleukin-4 / Q000096:biosynthesis; D015848:Interleukin-5 / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009124:Muscle Proteins / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D010047:Ovalbumin / Q000494:pharmacology; D011014:Pneumonia; D011657:Pulmonary Eosinophilia / Q000209:etiology* / Q000473:pathology; D013234:Stem Cells / Q000473:pathology
chemical_list: D002135:Calcium-Binding Proteins; C511512:DSCR1 protein, mouse; D015848:Interleukin-5; D047908:Intracellular Signaling Peptides and Proteins; D009124:Muscle Proteins; D015847:Interleukin-4; D010047:Ovalbumin; D019703:Calcineurin