The pathological findings suggested that suppression of the activated CXCL10-CXCR3 axis in the exocrine as well as the endocrine pancreas is a novel therapeutic target in FT1DM and possibly in enterovirus-associated acute-onset type 1 diabetes.
IP-10 and its receptor, CXCR3, appear to contribute to the pathogenesis of many autoimmune diseases, organ specific (such as type 1 diabetes, Graves' disease and ophthalmopathy), or systemic (such as systemic lupus erythematosus, mixed cryoglobulinemia, Sjogren syndrome, or systemic sclerosis).
The CXCL10 serum levels were not elevated in children at onset of type 1 diabetes and there was a considerable overlap between the groups with 99 (8-498) pg/ml in serum from children with type 1 diabetes, 120 (17-538) pg/ml in serum from controls, and 117 (7-448) pg/ml in siblings of the children with type 1 diabetes.
We therefore sought to determine whether exendin-4 decreases expression of the gene encoding chemokine (C-X-C motif) ligand (CXCL)10, which plays a role in initiating insulitis in type 1 diabetes.
Following TCR stimulation, T1DM displayed significantly greater mRNA responses than CL for TNFSF5, 7, 9, and CCL8, and CXCL10; TNFSF9, CCL8, and CXCL10 were also significantly higher in T1DM than OW; no difference was observed between OW and CL.
Although we did not find an association of the CXCL9 and CXCL10 polymorphisms with type 1 diabetes in the German population, we cannot discard their role in other populations or other autoimmune diseases.
Also, circulating and monocytic levels of IP-10 in patients with T1DM with and without microvascular complications (T1DM-MV and T1DM) and controls (C) was assessed.
Type 1 diabetes is considered to be a Th1-dominant autoimmune disease, and a suppressive effect of CXCL10 neutralization on diabetes development has been reported in a cyclophosphamide-induced accelerated diabetes model through induction of beta cell proliferation.
-to: Nicoletti F, Conget L, Di Mauro M et al. (2002) Serum concentrations of the interferon-alpha-inducible chemokine IP-10/CXCL10 are augmented in both newly-diagnosed Type I diabetes mellitus patients and subjects at risk of developing the disease. Diabetologia 45:1107-1110.