Activation of the adenosine A2A receptor attenuates experimental autoimmune myasthenia gravis severity.

The adenosine A2A receptor (A2AR) is the major cellular adenosine receptor commonly associated with immunosuppression. Here, we investigated whether A2AR activation holds the potential for impacting the severity of experimental autoimmune myasthenia gravis (EAMG) induced following immunization of Lewis rats with the acetylcholine receptor (AChR) R97-116 peptide. This report demonstrates reduced A2AR expression by both T cells and B cells residing in spleen and lymph nodes following EAMG induction. A2AR stimulation inhibited anti-AChR antibody production and proliferation of AChR-specific lymphocytes in vitro. Inhibition was blocked with the A2AR antagonists or protein kinase A inhibitor. We also determined that the development of EAMG was accompanied by a T-helper cell imbalance that could be restored following A2AR stimulation that resulted in increased Treg cell levels and a reduction in Th1-, Th2-, and Th17-cell subtypes. An EAMG-preventive treatment regimen was established that consisted of (2-(p-(2-carbonylethyl)phenylethylamino)-5-N-ethylcarboxamidoadenosine) (CGS21680; A2AR agonist) administration 1 day prior to EAMG induction. Administration of CGS21680 29 days post EAMG induction (therapeutic treatment) also ameliorated disease severity. We conclude that A2AR agonists may represent a new class of compounds that can be developed for use in the treatment of myasthenia gravis or other T-cell- and B-cell-mediated autoimmune diseases.

Li N ，Mu L ，Wang J ，Zhang J ，Xie X ，Kong Q ，Tang W ，Yao X ，Liu Y ，Wang L ，Wang G ，Wang D ，Jin L ，Sun B ，Li H ... -  《-》

Suppression of experimental myasthenia gravis by a B-cell epitope-free recombinant acetylcholine receptor.

Yi HJ ，Chae CS ，So JS ，Tzartos SJ ，Souroujon MC ，Fuchs S ，Im SH ... -  《MOLECULAR IMMUNOLOGY》

ATRA alters humoral responses associated with amelioration of EAMG symptoms by balancing Tfh/Tfr helper cell profiles.

All-trans retinoic acid (ATRA) is a vitamin A metabolite with diverse immunomodulatory actions used therapeutically in the treatment of some autoimmune diseases. However, the effects that ATRA may have on diminishing myasthenia gravis (MG) symptoms remain undefined. This study investigated the effect of ATRA on experimental autoimmune myasthenia gravis (EAMG) in vivo and in vitro. Data presented in this study demonstrated that intraperitoneal injection of ATRA ameliorated EAMG pathology in rats associated with reduced total anti-acetylcholine receptor (AChR) serum IgG levels. We observed that EAMG development was accompanied by an increase in follicular helper T cells (Tfh, defined as CD4(+)CXCR5(+)ICOS(high)) and a decrease of follicular regulatory T cells (Tfr, defined as CD4(+)Foxp3(+)CXCR5(+)ICOS(median)) and that the Tfh:Tfr ratio was altered following ATRA administration. In addition, ATRA treatment restored the Th1/Th2/Th17/Treg balance. In vitro, ATRA inhibited AChR-specific cell proliferation and eliciting apoptosis in these cells without affecting the cell cycle. ATRA also altered the Th distribution in animals presenting with EAMG resulting in a reduction in Th1/Th17/Tfh cells and increasing the number of Th2/Treg/Tfr cell types. These results suggested that ATRA reduced EAMG severity by regulating Th cell profiles thereby providing new insights into the development of novel MG (or related) therapies.

Xie X ，Mu L ，Yao X ，Li N ，Sun B ，Li Y ，Zhan X ，Wang X ，Kang X ，Wang J ，Liu Y ，Zhang Y ，Wang G ，Wang D ，Liu X ，Kong Q ，Li H ... -  《-》

The limitation of IL-10-exposed dendritic cells in the treatment of experimental autoimmune myasthenia gravis and myasthenia gravis.

Xiao BG ，Duan RS ，Zhu WH ，Lu CZ ... -  《CELLULAR IMMUNOLOGY》

Protective potential of experimental autoimmune myasthenia gravis in Lewis rats by IL-10-modified dendritic cells.

Duan RS ，Adikari SB ，Huang YM ，Link H ，Xiao BG ... -  《NEUROBIOLOGY OF DISEASE》