0000000000919385
AUTHOR
Junda M. Kel
TGF-β inhibitor Smad7 regulates dendritic cell-induced autoimmunity
TGF-β is an anti-inflammatory cytokine whose signaling is negatively controlled by Smad7. Previously, we established a role for Smad7 in the generation of autoreactive T cells; however, the function of Smad7 in dendritic cells (DCs) remains elusive. Here, we demonstrate that DC-specific Smad7 deficiency resulted in elevated expression of the transcription factors Batf3 and IRF8, leading to increased frequencies of CD8(+)CD103(+) DCs in the spleen. Furthermore, Smad7-deficient DCs expressed higher levels of indoleamine 2,3-dioxygenase (IDO), an enzyme associated with tolerance induction. Mice devoid of Smad7 specifically in DCs are resistant to the development of experimental autoimmune ence…
DC specific Smad7 deficiency promotes differentiation of tolerogenic DCs able to attenuate EAE
The immune network is a complex system for host defenses comprising various types of inflammatory and regulatory cells. Autoimmune diseases occur because of dysregulation in homeostasis caused by imbalance of these cells. The pattern of imbalance depends on the disease. Most autoimmune diseases are chronic, and the mechanism underlying this chronic nature is yet to be determined. Monoclonal antibody therapy is highly specific to the molecules targeted and is therefore highly effective. However, this therapy cannot be applied to all autoimmune diseases, and even the most effective therapy is incapable of completely inhibiting disease activity. Antigen-specific therapies have the ability to i…