Inflammation and decreased immunoregulation characterize the leptin receptor deficient (db/db) mouse model of type II diabetes. (173.12)

• Published in: The Journal of immunology (1950) Vol. 188; no. 1_Supplement; pp. 173 - 173.12
• Main Authors: Hardie, Virginia, Wheeler, Matthew, Harms, Robert, Boyer, Craig, Thiessen, Kevin, George, Nick, Targy, Natalie, Lorenzo, Kristina, Mercer, David, Sarvetnick, Nora
• Format: Journal Article
• Language: English
• Published: 01.05.2012
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.188.Supp.173.12

Abstract Type II diabetes is an inflammatory disease marked by chronic immune activation. Our goal is to describe the fundamental distinctions in the immune system of the db/db mouse. Serum was collected for a 58-factor immunoassay. Splenic leukocytes were isolated for six panels of flow cytometry to examine immune subsets and activation states. Db/db mice exhibit higher levels of proinflammatory factors such as C-reactive protein, granulocyte chemotactic protein-2, monocyte chemotactic protein-1, macrophage inflammatory protein-2, IL1α, and T-RANTES and lower levels in regulatory IL10. Flow cytometry data revealed upregulation of the adhesion molecule CD11b on neutrophils, monocytes and macrophages. Macrophages also expressed increased levels of costimulatory molecule CD80. Inflammatory DC were increased while regulatory DC were decreased. Pre-germinal center B cells were decreased. Plasma and memory B cells were increased with an increase in CD22 maturity marker. FoxP3+ T regs were decreased with a reciprocal increase in CD127. Total CD8 T cells were increased with greater naive populations. Unactivated NK cells were increased, and all NK populations had decreased Ly49H and KLRG1. Above results were significant with p<0.05. Baseline immune activation in db/db mice is marked by increased circulating proinflammatory factors, decreased circulating regulatory factors, increased activation of innate and humoral immunity, and suppressed regulatory and cellular immunity.