ABSTRACT
Drug-induced liver injury (DILI) is often caused by innate and adaptive host immune responses. Characterization of inflammatory infiltrates in the liver may improve understanding of the underlying pathogenesis of DILI. This study aimed to enumerate and characterize leucocytes infiltrating liver tissue from subjects with acute DILI (n = 32) versus non-DILI causes of acute liver injury (n = 25). Immunostains for CD11b/CD4 (Kupffer and T helper cells), CD3/CD20 (T and B cells) and CD8/CD56 [T cytotoxic and natural killer (NK) cells] were evaluated in biopsies from subjects with acute DILI, either immunoallergic (IAD) or autoimmune (AID) and idiopathic autoimmune (AIH) and viral hepatitis (VH) and correlated with clinical and pathological features. All biopsies showed numerous CD8(+) T cells and macrophages. DILI cases had significantly fewer B lymphocytes than AIH and VH and significantly fewer NK cells than VH. Prominent plasma cells were unusual in IAD (three of 10 cases), but were associated strongly with AIH (eight of nine) and also observed in most with AID (six of nine). They were also found in five of 10 cases with VH. Liver biopsies from subjects with DILI were characterized by low counts of mature B cells and NK cells in portal triads in contrast to VH. NK cells were found only in cases of VH, whereas AIH and VH both showed higher counts of B cells than DILI. Plasma cells were associated most strongly with AIH and less so with AID, but were uncommon in IAD.
Subject(s)
Chemical and Drug Induced Liver Injury/immunology , Chemical and Drug Induced Liver Injury/pathology , Hepatitis, Autoimmune/immunology , Hepatitis, Autoimmune/pathology , Hepatitis, Viral, Human/immunology , Hepatitis, Viral, Human/pathology , Acute Disease , Adolescent , Adult , Aged , Aged, 80 and over , Antigens, CD/immunology , B-Lymphocytes/immunology , B-Lymphocytes/pathology , CD8-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/pathology , Child , Female , Humans , Killer Cells, Natural/immunology , Killer Cells, Natural/pathology , Kupffer Cells/immunology , Kupffer Cells/pathology , Male , Middle AgedABSTRACT
Integrins are alphabeta heterodimeric receptors that connect the extracellular environment with intracellular signaling events. Integrins are important for normal development and function, but are also involved in the pathogenesis of diseases including cancer, autoimmunity and heart disease. We will review the present data on a family of integrins, the collagen receptors that include the alpha1beta1, alpha2beta1, alpha1beta1 and alpha1beta1 integrins. We will describe the knowledge gained from genetic deletion of each integrin in animal models. Mice lacking any single collagen receptor display no overt defect. However, studies using the alpha1beta1 and alpha2beta1 integrin-deficient mice indicate that these receptors play an important role in innate immunity, inflammation and autoimmunity. Finally, we will elucidate the interesting and sometimes overlapping roles for alpha1beta1 and alpha2beta1 integrins in disease and will propose potential stategies to therapeutically target these receptors to alleviate or treat disease.
