Differential lipid signaling from CD4 and CD8 T cells contributes to type 1 diabetes development.

Introduction: We reported that Ca-independent phospholipase Aβ (iPLAβ)-derived lipids (iDLs) contribute to type 1 diabetes (T1D) onset. As CD4 and CD8 T cells are critical in promoting β-cell death, we tested the hypothesis that iDL signaling from these cells participates in T1D development.

Methods: CD4 and CD8 T cells from wild-type non-obese diabetic () and .

The Impact of the Ca-Independent Phospholipase Aβ (iPLAβ) on Immune Cells.

The Ca-independent phospholipase Aβ (iPLAβ) is a member of the PLA family that has been proposed to have roles in multiple biological processes including membrane remodeling, cell proliferation, bone formation, male fertility, cell death, and signaling. Such involvement has led to the identification of iPLAβ activation in several diseases such as cancer, cardiovascular abnormalities, glaucoma, periodontitis, neurological disorders, diabetes, and other metabolic disorders. More recently, there has been heightened interest in the role that iPLAβ plays in promoting inflammation.

Macrophage polarization is linked to Ca-independent phospholipase Aβ-derived lipids and cross-cell signaling in mice.

Phospholipases A (PLAs) catalyze hydrolysis of the -2 substituent from glycerophospholipids to yield a free fatty acid (i.e., arachidonic acid), which can be metabolized to pro- or anti-inflammatory eicosanoids.

iPLAβ and its role in male fertility, neurological disorders, metabolic disorders, and inflammation.

The Ca-independent phospholipases, designated as group VI iPLAs, also referred to as PNPLAs due to their shared homology with patatin, include the β, γ, δ, ε, ζ, and η forms of the enzyme. The iPLAs are ubiquitously expressed, share a consensus GXSXG catalytic motif, and exhibit organelle/cell-specific localization. Among the iPLAs, iPLAβ has received wide attention as it is recognized to be involved in membrane remodeling, cell proliferation, cell death, and signal transduction.