Acetylation and deacetylation of the 9-OH position of sialic acid may serve as a rheostat controlling the strength of B cell antigen receptor responses in vivo, by modulating the activity of CD22, an inhibitory receptor of the Siglec family. Acetylation of sialic acid regulates other Siglecs and may potentially influence other aspects of immune regulation in immune cells other than B lymphocytes. The enzymes that regulate these acetylation and deacetylation events are potentially important targets for therapeutic intervention in immunological disorders, particularly humoral autoimmune disorders. Although the identity of the sialyl 9-O-acetyl esterase has been established and the consequences of the loss of this enzyme have been examined, the crucial sialyl 9-0-acetyl transferase remains to be characterized and cloned. We plan to utilize a cell-based assay to identify and characterize this sialyl 9-O-acetyl transferase. This cell-based assay will be used in conjunction with post-transcriptional gene silencing to identify genes that contribute to 9-O-acetylation of sialic acid. Lentiviral shRNA libraries will be used for both a candidate gene knockdown approach followed by an arrayed library strategy if necessary. The sialyl 9-O-acetyl transferase is a potential modulator of important inhibitory receptors in the immune system. Identifying and characterizing this enzyme may provide an important and novel target for the therapy of autoimmune and allergic disorders. The gene that codes for an enzyme that controls the strength of the immune response will be studied. This gene may be an important target for the treatment of lupus and other related diseases. ? ? ?
| Pillai, Shiv; Cariappa, Annaiah; Pirnie, Stephan P (2009) Esterases and autoimmunity: the sialic acid acetylesterase pathway and the regulation of peripheral B cell tolerance. Trends Immunol 30:488-93 |
| Cariappa, Annaiah; Takematsu, Hiromu; Liu, Haoyuan et al. (2009) B cell antigen receptor signal strength and peripheral B cell development are regulated by a 9-O-acetyl sialic acid esterase. J Exp Med 206:125-38 |
| Brainard, Diana M; Seung, Edward; Frahm, Nicole et al. (2009) Induction of robust cellular and humoral virus-specific adaptive immune responses in human immunodeficiency virus-infected humanized BLT mice. J Virol 83:7305-21 |
