Differential Effect of IL-27 on Developing versus Committed Th17 Cells. Export

@article{citeulike:5882619, abstract = {IL-27 counters the effect of TGF-beta+IL-6 on naive CD4(+) T cells, resulting in near complete inhibition of de novo Th17 development. In contrast, little is known about the effect of IL-27 on already differentiated Th17 cells. A better understanding of how IL-27 regulates these cells is needed to evaluate the therapeutic potential of IL-27 in Th17 cells-associated diseases. In this study, we show that IL-27 had surprisingly little effect on committed Th17 cells, despite its expression of a functional IL-27R. Contrary to de novo differentiation of Th17 cells, IL-27 did not suppress expression of retinoid-related orphan receptor (ROR)gammat or RORalpha in committed Th17 cells. Consistent with this finding, the frequency of committed Th17 cells and their cytokine secretion remained unaffected by IL-27. Both memory Th17 cells (CD4(+)CD25(-)CD62L(low)) that developed in vivo and encephalitogenic Th17 cells infiltrating the CNS of mice developing experimental autoimmune encephalomyelitis produced similar amounts of IL-17A when reactivated with IL-23 in the absence and presence of exogenous IL-27. Finally, IL-27 failed to suppress encephalitogenicity of Th17 cells in an adoptive transfer of experimental autoimmune encephalomyelitis. Analysis ex vivo of transferred Th17 cells in the spleen and CNS of recipient mice showed that cells retained similar phenotype irrespective of whether cells were treated or not with IL-27. Our data demonstrate that in contrast to inhibition of de novo differentiation of Th17 cells, IL-27 has little or no effect on committed Th17 cells. These findings indicate that therapeutic applications of IL-27 might have a limited efficacy in inflammatory conditions where aggressive Th17 responses have already developed.}, author = {El-Behi, Mohamed and Ciric, Bogoljub and Yu, Shuo and Zhang, Guang-Xian X. and Fitzgerald, Denise C. and Rostami, Abdolmohamad}, citeulike-article-id = {5882619}, citeulike-linkout-0 = {http://dx.doi.org/10.4049/jimmunol.0900735}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/19786534}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=19786534}, day = {28}, doi = {10.4049/jimmunol.0900735}, issn = {1550-6606}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, keywords = {cell\_differentiation, commitment, il-27, th17\_cells}, month = {September}, posted-at = {2009-10-03 21:58:28}, priority = {2}, title = {Differential Effect of IL-27 on Developing versus Committed Th17 Cells.}, url = {http://dx.doi.org/10.4049/jimmunol.0900735}, year = {2009} }

TY - JOUR ID - citeulike:5882619 L3 - citeulike-article-id:5882619 N2 - IL-27 counters the effect of TGF-beta+IL-6 on naive CD4(+) T cells, resulting in near complete inhibition of de novo Th17 development. In contrast, little is known about the effect of IL-27 on already differentiated Th17 cells. A better understanding of how IL-27 regulates these cells is needed to evaluate the therapeutic potential of IL-27 in Th17 cells-associated diseases. In this study, we show that IL-27 had surprisingly little effect on committed Th17 cells, despite its expression of a functional IL-27R. Contrary to de novo differentiation of Th17 cells, IL-27 did not suppress expression of retinoid-related orphan receptor (ROR)gammat or RORalpha in committed Th17 cells. Consistent with this finding, the frequency of committed Th17 cells and their cytokine secretion remained unaffected by IL-27. Both memory Th17 cells (CD4(+)CD25(-)CD62L(low)) that developed in vivo and encephalitogenic Th17 cells infiltrating the CNS of mice developing experimental autoimmune encephalomyelitis produced similar amounts of IL-17A when reactivated with IL-23 in the absence and presence of exogenous IL-27. Finally, IL-27 failed to suppress encephalitogenicity of Th17 cells in an adoptive transfer of experimental autoimmune encephalomyelitis. Analysis ex vivo of transferred Th17 cells in the spleen and CNS of recipient mice showed that cells retained similar phenotype irrespective of whether cells were treated or not with IL-27. Our data demonstrate that in contrast to inhibition of de novo differentiation of Th17 cells, IL-27 has little or no effect on committed Th17 cells. These findings indicate that therapeutic applications of IL-27 might have a limited efficacy in inflammatory conditions where aggressive Th17 responses have already developed. JF - Journal of immunology (Baltimore, Md. : 1950) SN - 1550-6606 TI - Differential Effect of IL-27 on Developing versus Committed Th17 Cells. KW - cell_differentiation KW - commitment KW - il-27 KW - th17_cells AU - El-Behi, Mohamed AU - Ciric, Bogoljub AU - Yu, Shuo AU - Zhang, Guang-Xian AU - Fitzgerald, Denise AU - Rostami, Abdolmohamad PY - 2009/09/28/ UR - http://dx.doi.org/10.4049/jimmunol.0900735 ER -