TY - JOUR A2 - Seger, Rony AU - Ruppert, Shannon M. AU - Falk, Ben A. AU - Long, S. Alice AU - Bollyky, Paul L. PY - 2015 DA - 2015/09/10 TI - Regulatory T Cells Resist Cyclosporine-Induced Cell Death via CD44-Mediated Signaling Pathways SP - 614297 VL - 2015 AB - Cyclosporine A (CSA) is an immunosuppressive agent that specifically targets T cells and also increases the percentage of pro-tolerogenic CD4+Foxp3+ regulatory T cells (Treg) through unknown mechanisms. We previously reported that CD44, a receptor for the extracellular matrix glycosaminoglycan hyaluronan (HA), promotes Treg stability in IL-2-low environments. Here, we asked whether CD44 signaling also promotes Treg resistance to CSA. We found that CD44 cross-linking promoted Foxp3 expression and Treg viability in the setting of CSA treatment. This effect was IL-2 independent but could be suppressed using sc-355979, an inhibitor of Stat5-phosphorylation. Moreover, we found that inhibition of HA synthesis impairs Treg homeostasis but that this effect could be overcome with exogenous IL-2 or CD44-cross-linking. Together, these data support a model whereby CD44 cross-linking by HA promotes IL-2-independent Foxp3 expression and Treg survival in the face of CSA. SN - 1687-8876 UR - https://doi.org/10.1155/2015/614297 DO - 10.1155/2015/614297 JF - International Journal of Cell Biology PB - Hindawi Publishing Corporation KW - ER -