Granulocyte-dendritic cell unbalance in the non-obese diabetic mice.
Several investigators, including ourselves, have reported lower yield of GM-CSF bone marrow-derived dendritic cells (DC) with altered MHC class II and co-stimulatory molecules expression in the non-obese diabetic (NOD) mice. However, whether this defect was intrinsic to the DC lineage and/or related to abnormal expansion of other cell types responding to GM-CSF remained an opened issue. We performed phenotypical and morphological analysis of cells from GM-CSF-supplemented-bone marrow-cultures and of freshly isolated bone marrow and blood cells from unmanipulated prediabetic NOD mice. The results show a heretofore undescribed bias towards generation of granulocytes in NOD mice, concomitant with quantitative and qualitative alterations of the DC lineage in both the bone marrow and the blood of this mouse strain. We propose that increased generation of granulocytes in NOD mice might contribute to autoimmunity. First, high numbers of granulocytes per se might favor inflammatory environment. Second, granulocytes, by interfering with DC development, might favor unbalanced antigen presenting cell function leading to T cell autoimmunity.
Morin
Joëlle
J
Laboratoire d'Immunologie, Génétique et Traitement des Maladies Métaboliques et du Diabète, Inserm U 561, Hopital Saint-Vincent-de-Paul, Paris, France.
Chimènes
Amélie
A
Boitard
Christian
C
Berthier
Rolande
R
Boudaly
Sarah
S
D000818:Animals; D001853:Bone Marrow / Q000276:immunology; D039481:CD11b Antigen / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology / Q000494:pharmacology; D006098:Granulocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D016688:Mice, Inbred NOD; D038042:Myelopoiesis / Q000187:drug effects
D039481:CD11b Antigen; D000949:Histocompatibility Antigens Class II; D015847:Interleukin-4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor