Gut immune deficits in LEW.1AR1-iddm rats partially overcome by feeding a diabetes-protective diet.
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.
['Crookshank|Jennifer A|JA|', 'Patrick|Christopher|C|', 'Wang|Gen-Sheng|GS|', 'Noel|J Ariana|JA|', 'Scott|Fraser W|FW|']
D000818:Animals D002364:Caseins D016207:Cytokines D003922:Diabetes Mellitus, Type 1 D004032:Diet D003927:Diet, Diabetic D004064:Digestive System D004195:Disease Models, Animal D002523:Edible Grain D005434:Flow Cytometry D015870:Gene Expression D006706:Homeostasis D006801:Humans D007109:Immunity D018836:Inflammation Mediators D007371:Interferon-gamma D007583:Jejunum D008264:Macrophages D011913:Rats, Inbred BB D011917:Rats, Inbred Lew D020133:Reverse Transcriptase Polymerase Chain Reaction D013601:T-Lymphocytes D050378:T-Lymphocytes, Regulatory D014886:Weaning
gut immunity diet type 1 diabetes M2 macrophage regulatory T cell