Abstract
Abstract Sickle cell disease, SCD, is an inherited blood disorder characterized by hardened, sticky C-shaped RBCs is a major cause of morbidity and mortality. It is the most prevalent genetic disease affecting 1/500 African Americans and 1/36000 Hispanics Americans, most residing in southeastern Virginia. Severe, frequent infections occur as a result of immune dysregulation associated with disease progression, impairing both innate and adaptive immunity. APCs such as DCs, B cells and macrophages express MHC II bind antigen that is recognized by TCR expressed on CD4+ Th cells. Thus, the interaction between receptor-ligand clusters on Th and APCs led to the activation of naïve CD4+ Th cells, stimulating the release of cytokines that influenced the activity of many cell types, including the NKT, CD8+ CTLs and the APCs that activated them. A “humanized” sickle mouse model of SCD was created by generating bone marrow chimeras using sickling mice donors and Pepboy recipients. We recently found that the transition from SPF to ‘dirty’, conventional, housing significantly dysregulated the immune system. These changes were characterized by a hyper-inflammatory state with the activation of innate-immune response, upregulation of TLR4, and loss of antigen-presentation machinery, loss of MHC II expression, with disease progression. Results indicate the loss of MHC II expression on APCs from various tissue of sickle mouse with the disease progression.
Published Version
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