title: Distinct signaling pathways regulate TLR2 co-stimulatory function in human T cells.
abstract: Toll-like receptor 2 (TLR2) serves as a co-stimulatory receptor for human T cells by enhancing T cell receptor (TCR)-induced cytokine production and proliferation. However, it is unknown where signals from the TCR and TLR2 converge to enhance T cell activation. To address this gap, we examined changes in TCR-induced signaling following concurrent TLR2 activation in human T cells. Both proximal TCR-mediated signaling and early NFκB activation were not enhanced by TCR and TLR2 co-activation, potentially due to the association of TLR2 with TLR10. Instead, TLR2 co-induction did augment Akt and Erk1/Erk2 activation in human T cells. These findings demonstrate that TLR2 activates distinct signaling pathways in human T cells and suggest that alterations in expression of TLR2 co-receptors may contribute to aberrant T cell responses.
authors.affiliation: Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Nicole M
authors.initials: NM
authors.lastname: Chapman
authors.forename: Mahmood Y
authors.initials: MY
authors.lastname: Bilal
authors.forename: Noemi
authors.initials: N
authors.lastname: Cruz-Orcutt
authors.forename: Cory
authors.initials: C
authors.lastname: Knudson
authors.forename: Sofia
authors.initials: S
authors.lastname: Madinaveitia
authors.forename: Jonathan
authors.initials: J
authors.lastname: Light
authors.forename: Jon C D
authors.initials: JC
authors.lastname: Houtman
mesh_terms: D000328:Adult; D001782:Blood Donors; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D008213:Lymphocyte Activation; D008875:Middle Aged; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000378:metabolism*; D055815:Young Adult
chemical_list: D018925:Chemokines; D016207:Cytokines; D016328:NF-kappa B; D011948:Receptors, Antigen, T-Cell; D051195:Toll-Like Receptor 2; D051057:Proto-Oncogene Proteins c-akt; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D002118:Calcium