title: Hematopoietic not systemic impairment of Roquin expression accounts for intestinal inflammation in Roquin-deficient mice.
abstract: Roquin, an E3 ligase, is involved in curtailing autoimmune pathology as seen from studies using mice with mutated (Rc3h1(san/san)) or disrupted (Rc3h1(gt/gt)) Rc3h1 gene. The extent to which intestinal immunopathology is caused by insufficient Roquin expression in the immune system, or by Roquin impairment in non-hematopoietic cells, has not been determined. Using bone marrow cells from Rc3h1(gt/gt) mice transferred into irradiated normal mice (Rc3h1(gt/gt) → NL chimeras), we show that inflammation developed in the small intestine, kidney, lung, liver, and spleen. Proinflammatory cytokine levels were elevated in lamina propria lymphocytes (LPLs). Inflammation in the liver was accompanied by areas of hepatocyte apoptosis. Lung inflammation consisted of an influx of both T cells and B cells. Small intestinal LPLs had increased numbers of CD44(hi), CD62L(lo), KLRG1(+), ICOS(+) short-lived effector cells, indicating an influx of activated T cells. Following oral infection with L. monocytogenes, Rc3h1(gt/gt) → NL chimeras had more liver pathology and greater numbers of bacteria in the Peyer's patches than NL → NL chimeras. These findings demonstrate that small intestinal inflammation in Rc3h1(san/san) and Rc3h1(gt/gt) mice is due to a failure of Roquin expression in the immune system and not to insufficient systemic Roquin expression.
authors.affiliation: Department of Diagnostic and Biomedical Sciences, School of Dentistry, The University of Texas Health Science Center at Houston, Houston, TX 77054 USA.
authors.forename: Dina
authors.initials: D
authors.lastname: Montufar-Solis
authors.affiliation: Department of Diagnostic and Biomedical Sciences, School of Dentistry, The University of Texas Health Science Center at Houston, Houston, TX 77054 USA.
authors.forename: Nadarajah
authors.initials: N
authors.lastname: Vigneswaran
authors.affiliation: Department of Diagnostic and Biomedical Sciences, School of Dentistry, The University of Texas Health Science Center at Houston, Houston, TX 77054 USA.
authors.forename: Niyati
authors.initials: N
authors.lastname: Nakra
authors.affiliation: Department of Diagnostic and Biomedical Sciences, School of Dentistry, The University of Texas Health Science Center at Houston, Houston, TX 77054 USA.
authors.forename: Jeremy S
authors.initials: JS
authors.lastname: Schaefer
authors.affiliation: Department of Diagnostic and Biomedical Sciences, School of Dentistry, The University of Texas Health Science Center at Houston, Houston, TX 77054 USA.
authors.forename: John R
authors.initials: JR
authors.lastname: Klein
mesh_terms: D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism; D053148:Caspase 3; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004751:Enteritis / Q000097:blood* / Q000235:genetics* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015870:Gene Expression; D006410:Hematopoiesis / Q000235:genetics*; D007156:Immunologic Memory; D016130:Immunophenotyping; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism; D007421:Intestine, Small / Q000378:metabolism / Q000473:pathology; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D010581:Peyer's Patches / Q000276:immunology / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000172:deficiency / Q000235:genetics*
chemical_list: D000954:Antigens, Surface; D016207:Cytokines; D018836:Inflammation Mediators; C501406:Rc3h1 protein, mouse; D044767:Ubiquitin-Protein Ligases; D053148:Caspase 3