Sarcoidosis is a Th1/Th17 multisystem disorder: wider implications response

We would like to thank Dr. Parisinos for his letter and interest in our study on the role of Th17 cells in sarcoidosis.[1] His recent report on the development of sarcoidosis in two patients affected by Crohn’s disease (CD) and treated with natalizumab [2] further highlights the deep link existing between the immune pathogenesis of the two disorders. In fact, sarcoidosis and Crohn’s disease are both characterized by an abnormal immune response to still unknown factor(s) that ultimately leads to granuloma formation and tissue damage, and, additionally, in both diseases Th1 and Th17 cytokines coexist and exacerbate the local immune reactions. Interestingly but not surprisingly, the presence of IL-17 producing T cells further marks out immune-mediated and chronic inflammatory diseases that can coexist with sarcoidosis (systemic lupus erythematosus, autoimmune chronic hepatitis, multiple sclerosis, coeliac disease, ulcerative colitis). In this context, the use of natalizumab represents an intriguing biological variable not only for its direct function (i.e. the inhibition of the alpha4-mediated adhesion of leukocytes to their counter-receptors) but even for its effects on T cells, particularly the regulatory T cells (Tregs), that are expanded in patients treated with natalizumab.[3] Considering that in presence of proinflammatory cytokines, such as IL-6 (another cytokine shared by sarcoidosis and Crohn’s disease), Tregs convert into Th17 lymphocytes,[4] it could be very interesting to know the levels of Tregs and Th17 cells in the two CD patients described by Parisinos and colleagues.