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Indu Rekha Ramachandran, Jonathan Michael Levitt, Role of the SH2 domain-containing Phosphatase-1, SHP-1 in Dendritic Cell Activation (89.6), The Journal of Immunology, Volume 178, Issue 1_Supplement, April 2007, Page S149, https://doi.org/10.4049/jimmunol.178.Supp.89.6
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Abstract
SHP-1 is an SH2 domain containing phosphatase activated upon recruitment to inhibitory receptors through their immunotyrosine inhibitory motif domains. Once activated, SHP-1 can dephosphorylate a wide range of receptors (e.g. antigen, chemokine and cytokine receptors), as well as their downstream signaling molecules, dampening cellular signals. Although SHP-1 is highly expressed in dendritic cells (DCs), its role in DC signaling and function is not well defined. By blocking SHP-1 activity with shRNA or a phosphatase dead dominant negative mutant (dn), our studies in the murine DC line, D2SC/1 show that SHP-1 inhibited AP-1 activity, upon LPS stimulation but did not affect NFκB activity. This is in contrast to SHP-1 function in RAW264.7 macrophages where it inhibits both AP-1 and NFκB activity after LPS and/or IFNγ treatment. Further, phenotypic characterization of primary bone-marrow derived DCs from SHP-1 deficient motheaten viable (MeV) mice shows, surprisingly, that the MeV DCs have drastically lower and uninducible levels of MHC class II surface expression compared to wild-type DCs. We are currently investigating the mechanisms by which SHP-1 affects class II surface expression in DCs. Taken together, these studies elucidate differences between SHP-1 signaling in DCs and macrophages which may have bearing on their differential ability to modulate antigen presentation and subsequent T cell activation.
Supported by DOD New Investigator Award PC061027 to JL.
