PI3Kδ and PI3Kγ: partners in crime in inflammation in rheumatoid arthritis and beyond?

The phosphoinositide 3-kinase (PI3K) isoforms PI3Kδ and PI3Kγ generate lipid second messengers that control an array of signalling pathways for numerous immune-cell functions. Recent studies indicate that specific targeting of these PI3K isoforms could be beneficial for treating inflammatory diseases. Dysregulated signal transduction in innate and adaptive immune cells is known to be associated with the development of various autoimmune and inflammatory diseases. Consequently, targeting intracellular signalling of the pro-inflammatory cytokine network heralds hope for the next generation of anti-inflammatory drugs. Phosphoinositide 3-kinases (PI3Ks) generate lipid-based second messengers that control an array of intracellular signalling pathways that are known to have important roles in leukocytes. In light of the recent progress in the development of selective PI3K inhibitors, and the beneficial effects of these inhibitors in models of acute and chronic inflammatory disorders, we discuss the therapeutic potential of blocking PI3K isoforms for the treatment of rheumatoid arthritis and other immune-mediated diseases.