In summary, we have shown that SIRT1 activity regulates the FAK-dependent activation of transcription factors involved in proliferation, migration, and proinflammatory activation of yolk sac Mφ in chronic CD, and SIRT1 agonists offer a potential therapeutic approach to reprogram the proinflammatory Mφ and control chronic inflammatory pathology in CD. The gene discussed is PTK2; the disease is Cowden disease.