CD69 acts downstream of interferon-α/β to inhibit S1P1 and lymphocyte egress from lymphoid organs Export

@article{citeulike:540958, abstract = {Naive lymphocytes continually enter and exit lymphoid organs in a recirculation process that is essential for immune surveillance. During immune responses, the egress process can be shut down transiently1. When this occurs locally it increases lymphocyte numbers in the responding lymphoid organ; when it occurs systemically it can lead to immunosuppression as a result of the depletion of recirculating lymphocytes. Several mediators of the innate immune system are known to cause shutdown, including interferon / (IFN-/) and tumour necrosis factor2, 3, 4, 5, but the mechanism has been unclear. Here we show that treatment with the IFN-/ inducer polyinosine polycytidylic acid (hereafter 'poly(I:C)') inhibited egress by a mechanism that was partly lymphocyte-intrinsic. The transmembrane C-type lectin CD69 was rapidly induced and CD69-/- cells were poorly retained in lymphoid tissues after treatment with poly(I:C) or infection with lymphocytic choriomeningitis virus. Lymphocyte egress requires sphingosine 1-phosphate receptor-1 (S1P1), and IFN-/ was found to inhibit lymphocyte responsiveness to S1P. By contrast, CD69-/- cells retained S1P1 function after exposure to IFN-/. In coexpression experiments, CD69 inhibited S1P1 chemotactic function and led to downmodulation of S1P1. In a reporter assay, S1P1 crosslinking led to co-crosslinking and activation of a CD69–CD3 chimaera. CD69 co-immunoprecipitated with S1P1 but not the related receptor, S1P3. These observations indicate that CD69 forms a complex with and negatively regulates S1P1 and that it functions downstream of IFN-/, and possibly other activating stimuli, to promote lymphocyte retention in lymphoid organs.}, author = {Shiow, Lawrence R. and Rosen, David B. and Brdi\v{c}kov\~{a}!`, Nad\v{e}\v{z}da and Xu, Ying and An, Jinping and Lanier, Lewis L. and Cyster, Jason G. and Matloubian, Mehrdad}, citeulike-article-id = {540958}, citeulike-linkout-0 = {http://dx.doi.org/10.1038/nature04606}, citeulike-linkout-1 = {http://dx.doi.org/10.1038/nature04606}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/16525420}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=16525420}, day = {08}, doi = {10.1038/nature04606}, issn = {0028-0836}, journal = {Nature}, keywords = {cd69, lymphocyte\_egress, type\_1\_ifn}, month = {March}, posted-at = {2008-07-30 01:32:02}, priority = {0}, publisher = {Nature Publishing Group}, title = {CD69 acts downstream of interferon-α/β to inhibit S1P1 and lymphocyte egress from lymphoid organs}, url = {http://dx.doi.org/10.1038/nature04606}, year = {2006} }

TY - JOUR ID - citeulike:540958 L3 - citeulike-article-id:540958 N2 - Naive lymphocytes continually enter and exit lymphoid organs in a recirculation process that is essential for immune surveillance. During immune responses, the egress process can be shut down transiently1. When this occurs locally it increases lymphocyte numbers in the responding lymphoid organ; when it occurs systemically it can lead to immunosuppression as a result of the depletion of recirculating lymphocytes. Several mediators of the innate immune system are known to cause shutdown, including interferon / (IFN-/) and tumour necrosis factor2, 3, 4, 5, but the mechanism has been unclear. Here we show that treatment with the IFN-/ inducer polyinosine polycytidylic acid (hereafter 'poly(I:C)') inhibited egress by a mechanism that was partly lymphocyte-intrinsic. The transmembrane C-type lectin CD69 was rapidly induced and CD69-/- cells were poorly retained in lymphoid tissues after treatment with poly(I:C) or infection with lymphocytic choriomeningitis virus. Lymphocyte egress requires sphingosine 1-phosphate receptor-1 (S1P1), and IFN-/ was found to inhibit lymphocyte responsiveness to S1P. By contrast, CD69-/- cells retained S1P1 function after exposure to IFN-/. In coexpression experiments, CD69 inhibited S1P1 chemotactic function and led to downmodulation of S1P1. In a reporter assay, S1P1 crosslinking led to co-crosslinking and activation of a CD69–CD3 chimaera. CD69 co-immunoprecipitated with S1P1 but not the related receptor, S1P3. These observations indicate that CD69 forms a complex with and negatively regulates S1P1 and that it functions downstream of IFN-/, and possibly other activating stimuli, to promote lymphocyte retention in lymphoid organs. JF - Nature SN - 0028-0836 TI - CD69 acts downstream of interferon-α/β to inhibit S1P1 and lymphocyte egress from lymphoid organs PB - Nature Publishing Group KW - cd69 KW - lymphocyte_egress KW - type_1_ifn AU - Shiow, Lawrence AU - Rosen, David AU - Brdičkovã¡, Naděžda AU - Xu, Ying AU - An, Jinping AU - Lanier, Lewis AU - Cyster, Jason AU - Matloubian, Mehrdad PY - 2006/03/08/ UR - http://dx.doi.org/10.1038/nature04606 ER -