Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011854 (type 1 diabetes)
 20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Expression of the erythrocyte complement receptor (C3bR = CR1 = CD35) and its genomic polymorphism (HindIII RFLP) was studied in a group of 80 patients with IDDM, 31 healthy siblings and 101 healthy blood donors. Defective CR1 expression was found in 26% of the patients with IDDM compared with 9% of the controls (P less than 0.05) and 0% of the siblings. The CR1 gene polymorphism of the IDDM patients did not significantly differ from that of the controls. The presence of a 6.9 kb (L) CR1 gene fragment was associated with a low CR1 expression in the patients (P less than 0.05) and especially in the controls (P less than 0.001). No significant association was found between the presence or absence of the HLA risk antigens for IDDM and CR1 expression. The results confirm that erythrocyte CR1 expression is genetically determined, but the CR1 deficiency associated with IDDM seems to be an acquired rather than a genetic phenomenon.
 ...
PMID:Normal C3b receptor (CR1) genomic polymorphism in patients with insulin-dependent diabetes mellitus (IDDM): is the low erythrocyte CR1 expression an acquired phenomenon? 135 45

Insulin-dependent diabetes mellitus (IDDM) is a disease with an autoimmune aetiology. The non-obese diabetic mouse is a good spontaneous animal model of the human disease, with IDDM developing in 50-80% of female mice by the age of 6 months. The disease can be transferred by splenic T cells from diabetic donors and is prevented by T-cell depletion. The mechanism(s) by which the beta cell is specifically destroyed is not known, but T cells and macrophages have both been implicated, based on the presence of macrophages in the infiltrated islet and the ability of chronic silica treatment to prevent disease. The monoclonal antibody 5C6 is specific for the myelomonocytic adhesion-promoting type-3 complement receptor (CR3 or CD11b/CD18) and does not bind to T cells. Here we show that blockade of macrophage CR3 in vivo prevents intra-islet infiltration by both macrophages and T cells and inhibits development of IDDM. We conclude that both T cells and macrophages have an essential role in the onset of IDDM.
 ...
PMID:Transfer of diabetes in mice prevented by blockade of adhesion-promoting receptor on macrophages. 225 Jul 18

The B7 family-related protein, V-set and Ig domain (VSIG4) / Z39Ig / complement receptor immunoglobulin (CRIg), is a new player in the regulation of immunity to infection and inflammation. The unique features of this receptor as compared with classical complement receptors, CR3 and CR4, have heralded the emergence of new concepts in the regulation of innate and adaptive immunity. Its selective expression in tissue macrophages and dendritic cells has been considered of importance in host defence and in maintaining tolerance against self-antigens. Although a major receptor for phagocytosis of complement opsonised bacteria, its array of emerging functions which incorporates the immune suppressive and anti-inflammatory action of the receptor have now been realised. Accumulating evidence from mouse experimental models indicates a potential role for CRIg in protection against bacterial infection and inflammatory diseases, such as rheumatoid arthritis, type 1 diabetes and systemic lupus erythematosus, and also in promotion of tumour growth. CRIg expression can be considered as a control point in these diseases, through which inflammatory mediators, including cytokines, act. The ability of CRIg to suppress cytotoxic T cell proliferation and function may underlie its promotion of cancer growth. Thus, the unique properties of this receptor open up new avenues for understanding of the pathways that regulate inflammation during infection, autoimmunity and cancer with the potential for new drug targets to be identified. While some complement receptors may be differently expressed in mice and humans, as well as displaying different properties, mouse CRIg has a structure and function similar to the human receptor, suggesting that extrapolation to human diseases is appropriate. Furthermore, there is emerging evidence in human conditions that CRIg may be a valuable biomarker in infection and immunity, inflammatory conditions and cancer prognosis.
 ...
PMID:Complement receptor immunoglobulin: a control point in infection and immunity, inflammation and cancer. 2704 7

How tissue-resident macrophages (TRM) impact adaptive immune responses remains poorly understood. We report novel mechanisms by which TRMs regulate T cell activities at tissue sites. These mechanisms are mediated by the complement receptor of immunoglobulin family (CRIg). Using animal models for autoimmune type 1 diabetes (T1D), we found that CRIg+ TRMs formed a protective barrier surrounding pancreatic islets. Genetic ablation of CRIg exacerbated islet inflammation and local T cell activation. CRIg exhibited a dual function of attenuating early T cell activation and promoting the differentiation of Foxp3+ regulatory (Treg) cells. More importantly, CRIg stabilized the expression of Foxp3 in Treg cells, by enhancing their responsiveness to interleukin-2. The expression of CRIg in TRMs was postnatally regulated by gut microbial signals and metabolites. Thus, environmental cues instruct TRMs to express CRIg, which functions as an immune checkpoint molecule to regulate adaptive immunity and promote immune tolerance.
 ...
PMID:CRIg, a tissue-resident macrophage specific immune checkpoint molecule, promotes immunological tolerance in NOD mice, via a dual role in effector and regulatory T cells. 2917 36