Defects in differentiation of bone-marrow derived dendritic cells of the BB rat are partly associated with IDDM2 (the lyp gene) and partly associated with other genes in the BB rat background.

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Defects in differentiation of bone-marrow derived dendritic cells of the BB rat are partly associated with IDDM2 (the lyp gene) and partly associated with other genes in the BB rat background. / Sommandas, V; Rutledge, E A; Van Yserloo, B; Fuller, J; Lernmark, Åke; Drexhage, H A.

In: Journal of Autoimmunity, Vol. 25, No. 1, 2005, p. 46-56.

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T1 - Defects in differentiation of bone-marrow derived dendritic cells of the BB rat are partly associated with IDDM2 (the lyp gene) and partly associated with other genes in the BB rat background.

AU - Sommandas, V

AU - Rutledge, E A

AU - Van Yserloo, B

AU - Fuller, J

AU - Lernmark, Åke

AU - Drexhage, H A

PY - 2005

Y1 - 2005

N2 - BB rats develop various organ-specific autoimmune diseases, e.g. autoimmune diabetes and thyroiditis and have proven important to dissect genetic factors that govern autoimmune disease development. The lymphopenia (lyp) gene (iddm2) is linked to autoimmune disease development and is a major genetic difference between diabetes-resistant (DR) and diabetes-prone (DP) BB rats. To study the effects of the lyp gene and other genes on dendritic cell (DC) differentiation from bone-marrow precursors, such differentiation was studied in BB-DP, BB-DR, Wistar and F344 control rats. DC of BB-DP rats showed a lower MHC class II expression as compared to BB-DR, Wistar and F344 rats. LPS-maturation did not restore this low MHC class II expression. DC of BB-DP rats also showed a poor capability to terminally differentiate into mature T cell stimulatory DC under the influence of LPS and produced significantly lower quantities of IL-10, yet these aberrancies were also found in BB-DR rats but did not occur in control rats. This study thus shows that various aberrancies exist in the differentiation of myeloid DC from bone-marrow precursors in the BB rat model of organ-specific autoimmunity. These aberrancies are multigenically determined and partly associated with iddm2 (lyp gene) and partly associated with other genes in the BB rat.

AB - BB rats develop various organ-specific autoimmune diseases, e.g. autoimmune diabetes and thyroiditis and have proven important to dissect genetic factors that govern autoimmune disease development. The lymphopenia (lyp) gene (iddm2) is linked to autoimmune disease development and is a major genetic difference between diabetes-resistant (DR) and diabetes-prone (DP) BB rats. To study the effects of the lyp gene and other genes on dendritic cell (DC) differentiation from bone-marrow precursors, such differentiation was studied in BB-DP, BB-DR, Wistar and F344 control rats. DC of BB-DP rats showed a lower MHC class II expression as compared to BB-DR, Wistar and F344 rats. LPS-maturation did not restore this low MHC class II expression. DC of BB-DP rats also showed a poor capability to terminally differentiate into mature T cell stimulatory DC under the influence of LPS and produced significantly lower quantities of IL-10, yet these aberrancies were also found in BB-DR rats but did not occur in control rats. This study thus shows that various aberrancies exist in the differentiation of myeloid DC from bone-marrow precursors in the BB rat model of organ-specific autoimmunity. These aberrancies are multigenically determined and partly associated with iddm2 (lyp gene) and partly associated with other genes in the BB rat.

KW - Dendritic cells

KW - BB rat

KW - lyp gene

U2 - 10.1016/j.jaut.2005.03.008

DO - 10.1016/j.jaut.2005.03.008

M3 - Article

C2 - 15922563

VL - 25

SP - 46

EP - 56

JO - Journal of Autoimmunity

JF - Journal of Autoimmunity

SN - 0896-8411

IS - 1

ER -