Immune dysregulation in a major hematologic disease (P3167)

• Published in: The Journal of immunology (1950) 2013-05, Vol.190 (1_Supplement), p.43-43.45
• Main Authors: Joshi, Sunil, Carey, David, Chavez-Suarez, Maria, Lang, Mark, Broyles, Robert, White, Gary
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.190.Supp.43.45

Sickle cell disease is the most prevalent genetic disease on the planet, and is a major cause of morbidity and death. Much of the morbidity in sickle cell disease is due to frequent, severe infections due to immune dysregulation associated with progression of disease. Both innate and adaptive immunity are impaired. It is well established that T and B cell responses are required for host defense. The CD4+ Th cells express TCR that recognize antigen bound to MHC II molecules expressed on APCs such as DCs, B cells and macrophages. Thus the cognate interaction between receptor-ligand clusters on Th and APCs led to the activation of naïve CD4+ Th cells causes them to release cytokines, which influence the activity of many cell types, including the NKT, CD8+ CTLs and the APCs that activated them. Using a “humanized” sickle mouse model of sickle cell disease, we recently found that the transition from SPF to ‘dirty’ (conventional) housing significantly dysregulated the immune-system. These changes are 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 class II expression) as the disease progresses. Specifically, our results indicate the loss of MHC II expression on APCs from various tissue of sickle mouse with the disease progression.