Abstract
Involvement of gut immune system has been implicated in the pathogenesis of type 1 diabetes. However, few studies have been performed on the gut mucosa from patients with type 1 diabetes. Thus, we characterized the stage of immune activation in jejunal biopsy samples from 31 children with type 1 diabetes by immunohistochemistry, in situ hybridization, and RT-PCR. We found enhanced expressions of HLA-DR, HLA-DP, and intercellular adhesion molecule-1 by immunohistochemistry even on structurally normal intestine of patients with type 1 diabetes and no signs of celiac disease. In addition, the densities of IL-1 alpha- and IL-4-positive cells detected by immunohistochemistry and IL-4 mRNA-expressing cells evaluated by in situ hybridization were increased in the lamina propria in patients with type 1 diabetes and normal mucosa. Instead, the densities of IL-2, gamma-interferon (IFN-gamma), and tumor necrosis factor alpha-positive cells, the density of IFN-gamma mRNA positive cells, and the amounts of IFN-gamma mRNA detected by RT-PCR correlated with the degree of celiac disease in patients with type 1 diabetes. Our study supports the hypothesis that a link exists between the gut immune system and type 1 diabetes.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Adolescent
-
Antibodies
-
Child
-
Child, Preschool
-
Diabetes Mellitus, Type 1 / genetics
-
Diabetes Mellitus, Type 1 / immunology*
-
Diabetes Mellitus, Type 1 / physiopathology*
-
Female
-
Gene Expression / immunology
-
Genotype
-
HLA Antigens / genetics
-
Histocompatibility Antigens Class II / analysis
-
Histocompatibility Antigens Class II / immunology
-
Humans
-
Immunohistochemistry
-
In Situ Hybridization
-
Intercellular Adhesion Molecule-1 / analysis
-
Intercellular Adhesion Molecule-1 / immunology
-
Interferon-gamma / genetics
-
Interleukin-1 / genetics
-
Interleukin-2 / genetics
-
Interleukin-4 / genetics
-
Intestinal Mucosa / immunology*
-
Jejunum / chemistry
-
Jejunum / immunology*
-
Ki-67 Antigen / analysis
-
Male
-
Phosphorus Radioisotopes
-
RNA, Messenger / analysis
-
Receptors, CCR4
-
Receptors, CCR5 / genetics
-
Receptors, Chemokine / genetics
-
Reverse Transcriptase Polymerase Chain Reaction
-
Tumor Necrosis Factor-alpha / genetics
Substances
-
Antibodies
-
CCR4 protein, human
-
HLA Antigens
-
Histocompatibility Antigens Class II
-
Interleukin-1
-
Interleukin-2
-
Ki-67 Antigen
-
Phosphorus Radioisotopes
-
RNA, Messenger
-
Receptors, CCR4
-
Receptors, CCR5
-
Receptors, Chemokine
-
Tumor Necrosis Factor-alpha
-
Intercellular Adhesion Molecule-1
-
Interleukin-4
-
Interferon-gamma