Sasanka Ramanadham, Ph.D., and researchers published “Selective Reduction of Ca2+-Independent Phospholipase A2β (iPLA2β)-Derived Lipid Signaling from Macrophages Mitigates Type 1 Diabetes Development"in the peer-reviewed journal Diabetes.

Ramanadham is a professor in the UAB Department of Cell, Developmental and Integrative Biology and a senior scientist in the UAB Comprehensive Diabetes Center. 

Macrophages are among the first immune cells that infiltrate the islets and recruit other immune cells and together they induce immune responses that promote autoimmune beta cell death. This causes marked decreases in insulin secretion and leads to Type 1 diabetes (T1D) development.

The Ramanadham Lab previously identified a critical role for select lipid signaling in inducing an inflammatory phenotype in macrophages. They hypothesized that such signaling from macrophages contributes to T1D onset. To test this, they generated a mouse model of T1D with reduced expression of the enzyme that generates the detrimental lipid signaling and assessed various diabetes-related outcomes using adoptive transfer, flow cytometry, qPCR, imaging, lipidomics, and ex-vivo approaches.

Their studies revealed for the first time that macrophage-derived lipid signaling plays a central role in T1D development. This was reflected in findings that mitigation of macrophage lipid signaling enhanced the anti-inflammatory phenotype of macrophages, leading to reduced inflammatory phenotype of CD4+ and CD8+ T-cells, and T1D incidence.

The researchers posit that their findings raise the possibility that targeting macrophage lipid signaling should be considered as a means to counter T1D development.

Other study authors include first author Abdulaziz Almutairi, Ph.D., Tayleur D. White, Ph.D., Daniel J. Stephenson, Ph.D., Benjamin D. Stephenson, Ying Gai-Tusing, Paran Goel, Daniel W. Phillips, Robert S. Welner, Ph.D., Xiaoyong Lei, Ph.D., Bruce D. Hammock, Ph.D., and Charles E. Chalfant, Ph.D.