[HTML][HTML] Specialized role of migratory dendritic cells in peripheral tolerance induction

J Idoyaga, C Fiorese, L Zbytnuik… - The Journal of …, 2013 - Am Soc Clin Investig
J Idoyaga, C Fiorese, L Zbytnuik, A Lubkin, J Miller, B Malissen, D Mucida, M Merad
The Journal of clinical investigation, 2013Am Soc Clin Investig
Harnessing DCs for immunotherapies in vivo requires the elucidation of the physiological
role of distinct DC populations. Migratory DCs traffic from peripheral tissues to draining
lymph nodes charged with tissue self antigens. We hypothesized that these DC populations
have a specialized role in the maintenance of peripheral tolerance, specifically, to generate
suppressive Foxp3+ Tregs. To examine the differential capacity of migratory DCs versus
blood-derived lymphoid-resident DCs for Treg generation in vivo, we targeted a self antigen …
Harnessing DCs for immunotherapies in vivo requires the elucidation of the physiological role of distinct DC populations. Migratory DCs traffic from peripheral tissues to draining lymph nodes charged with tissue self antigens. We hypothesized that these DC populations have a specialized role in the maintenance of peripheral tolerance, specifically, to generate suppressive Foxp3+ Tregs. To examine the differential capacity of migratory DCs versus blood-derived lymphoid-resident DCs for Treg generation in vivo, we targeted a self antigen, myelin oligodendrocyte glycoprotein, using antibodies against cell surface receptors differentially expressed in these DC populations. Using this approach together with mouse models that lack specific DC populations, we found that migratory DCs have a superior ability to generate Tregs in vivo, which in turn drastically improve the outcome of experimental autoimmune encephalomyelitis. These results provide a rationale for the development of novel therapies targeting migratory DCs for the treatment of autoimmune diseases.
The Journal of Clinical Investigation