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Gut immune deficits in LEW.1AR1‐ iddm rats partially overcome by feeding a diabetes‐protective diet
Author(s) -
Crookshank Jennifer A.,
Patrick Christopher,
Wang GenSheng,
Ariaoel J.,
Scott Fraser W.
Publication year - 2015
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.12457
Subject(s) - foxp3 , immune system , medicine , endocrinology , mesenteric lymph nodes , diabetes mellitus , t cell , biology , flow cytometry , lymph , immunology , pathology
Summary 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.