The endogenous danger signal, crystalline uric acid, signals for enhanced antibody immunity Export

@article{citeulike:4107982, abstract = {Studies have shown that the immune system can recognize self-antigens under conditions (eg, cell injury) in which the self-tissue might elaborate immune-activating endogenous danger signals. Uric acid (UA) is an endogenous danger signal recently identified to be released from dying cells. Prior work has shown that UA activates immune effectors of both the innate and adaptive immune system, including neutrophils and cytotoxic T-cell immunity. However, it was unclear whether UA could enhance antibody immunity, which was examined in this study. When added to dying tumor cells or with whole protein antigen, UA increased IgG1-based humoral immunity. Further, UA blocked growth of tumor in subsequent tumor challenge experiments, which depended on CD4, but not CD8, T cells. Sera derived from UA-treated animals enhanced tumor growth, suggesting it had little role in the antitumor response. UA did not signal for T-cell expansion or altered tumor-infiltrating leukocyte populations. Consistent with the lack of T-cell expansion, when applied to dendritic cells, UA suppressed T-cell growth factors but up-regulated B cell-activating cytokines. Understanding the nature of endogenous danger signals released from dying cells may aid in a better understanding of mechanisms of immune recognition of self. 10.1182/blood-2007-10-117184}, author = {Behrens, Marshall D. and Wagner, Wolfgang M. and Krco, Christopher J. and Erskine, Courtney L. and Kalli, Kimberly R. and Krempski, James and Gad, Ekram A. and Disis, Mary L. and Knutson, Keith L.}, citeulike-article-id = {4107982}, citeulike-linkout-0 = {http://dx.doi.org/10.1182/blood-2007-10-117184}, citeulike-linkout-1 = {http://bloodjournal.hematologylibrary.org/cgi/content/abstract/111/3/1472}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/18029553}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=18029553}, day = {1}, doi = {10.1182/blood-2007-10-117184}, journal = {Blood}, keywords = {acid, immunity, uric}, month = {February}, number = {3}, pages = {1472--1479}, posted-at = {2009-02-26 17:32:52}, priority = {2}, title = {The endogenous danger signal, crystalline uric acid, signals for enhanced antibody immunity}, url = {http://dx.doi.org/10.1182/blood-2007-10-117184}, volume = {111}, year = {2008} }

TY - JOUR ID - citeulike:4107982 L3 - citeulike-article-id:4107982 N2 - Studies have shown that the immune system can recognize self-antigens under conditions (eg, cell injury) in which the self-tissue might elaborate immune-activating endogenous danger signals. Uric acid (UA) is an endogenous danger signal recently identified to be released from dying cells. Prior work has shown that UA activates immune effectors of both the innate and adaptive immune system, including neutrophils and cytotoxic T-cell immunity. However, it was unclear whether UA could enhance antibody immunity, which was examined in this study. When added to dying tumor cells or with whole protein antigen, UA increased IgG1-based humoral immunity. Further, UA blocked growth of tumor in subsequent tumor challenge experiments, which depended on CD4, but not CD8, T cells. Sera derived from UA-treated animals enhanced tumor growth, suggesting it had little role in the antitumor response. UA did not signal for T-cell expansion or altered tumor-infiltrating leukocyte populations. Consistent with the lack of T-cell expansion, when applied to dendritic cells, UA suppressed T-cell growth factors but up-regulated B cell-activating cytokines. Understanding the nature of endogenous danger signals released from dying cells may aid in a better understanding of mechanisms of immune recognition of self. 10.1182/blood-2007-10-117184 IS - 3 JF - Blood EP - 1479 TI - The endogenous danger signal, crystalline uric acid, signals for enhanced antibody immunity VL - 111 SP - 1472 KW - acid KW - immunity KW - uric AU - Behrens, Marshall AU - Wagner, Wolfgang AU - Krco, Christopher AU - Erskine, Courtney AU - Kalli, Kimberly AU - Krempski, James AU - Gad, Ekram AU - Disis, Mary AU - Knutson, Keith PY - 2008/02/01/ UR - http://dx.doi.org/10.1182/blood-2007-10-117184 ER -