title: Gut immune deficits in LEW.1AR1-iddm rats partially overcome by feeding a diabetes-protective diet.
abstract: The gut immune system and its modification by diet have been implicated in the pathogenesis of type 1 diabetes (T1D). Therefore, we investigated gut immune status in non-diabetes-prone LEW.1AR1 and diabetes-prone LEW.1AR1-iddm rats and evaluated the effect of a low antigen, hydrolysed casein (HC)-based diet on gut immunity and T1D. Rats were weaned onto a cereal-based or HC-based diet and monitored for T1D. Strain and dietary effects on immune homeostasis were assessed in non-diabetic rats (50-60 days old) and rats with recent-onset diabetes using flow cytometry and immunohistochemistry. Immune gene expression was analysed in mesenteric lymph nodes (MLN) and jejunum using quantitative RT-PCR and PCR arrays. T1D was prevented in LEW.1AR1-iddm rats by feeding an HC diet. Diabetic LEW.1AR1-iddm rats had fewer lymphoid tissue T cells compared with LEW.1AR1 rats. The percentage of CD4(+)  Foxp3(+) regulatory T (Treg) cells was decreased in pancreatic lymph nodes (PLN) of diabetic rats. The jejunum of 50-day LEW.1AR1-iddm rats contained fewer CD3(+) T cells, CD163(+) M2 macrophages and Foxp3(+) Treg cells. Ifng expression was increased in MLN and Foxp3 expression was decreased in the jejunum of LEW.1AR1-iddm rats; Ifng/Il4 was decreased in jejunum of LEW.1AR1-iddm rats fed HC. PCR arrays revealed decreased expression of M2-associated macrophage factors in 50-day LEW.1AR1-iddm rats. Wheat peptides stimulated T-cell proliferation and activation in MLN and PLN cells from diabetic LEW.1AR1-iddm rats. LEW.1AR1-iddm rats displayed gut immune cell deficits and decreased immunoregulatory capacity, which were partially corrected in animals fed a low antigen, protective HC diet consistent with other models of T1D.
authors.affiliation: Ottawa Hospital Research Institute, Ottawa, ON, Canada.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Crookshank
authors.affiliation: Ottawa Hospital Research Institute, Ottawa, ON, Canada.|Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON, Canada.
authors.forename: Christopher
authors.initials: C
authors.lastname: Patrick
authors.affiliation: Ottawa Hospital Research Institute, Ottawa, ON, Canada.
authors.forename: Gen-Sheng
authors.initials: GS
authors.lastname: Wang
authors.affiliation: Ottawa Hospital Research Institute, Ottawa, ON, Canada.|Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON, Canada.
authors.forename: J Ariana
authors.initials: JA
authors.lastname: Noel
authors.affiliation: Ottawa Hospital Research Institute, Ottawa, ON, Canada.|Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON, Canada.|Department of Medicine, University of Ottawa, Ottawa, ON, Canada.
authors.forename: Fraser W
authors.initials: FW
authors.lastname: Scott
mesh_terms: D000818:Animals; D002364:Caseins / Q000276:immunology / Q000627:therapeutic use; D016207:Cytokines / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000178:diet therapy* / Q000235:genetics / Q000276:immunology*; D004032:Diet; D003927:Diet, Diabetic; D004064:Digestive System / Q000276:immunology* / Q000378:metabolism; D004195:Disease Models, Animal; D002523:Edible Grain / Q000276:immunology; D005434:Flow Cytometry; D015870:Gene Expression / Q000276:immunology; D006706:Homeostasis / Q000235:genetics / Q000276:immunology; D006801:Humans; D007109:Immunity / Q000235:genetics / Q000276:immunology; D018836:Inflammation Mediators / Q000276:immunology / Q000378:metabolism; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007583:Jejunum / Q000276:immunology / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D011913:Rats, Inbred BB; D011917:Rats, Inbred Lew; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism; D014886:Weaning
chemical_list: D002364:Caseins; D016207:Cytokines; D018836:Inflammation Mediators; C475729:casein hydrolysate; D007371:Interferon-gamma
keywords: M2 macrophage; diet; gut immunity; regulatory T cell; type 1 diabetes