title: Negative regulation of T cell activation and autoimmunity by the transmembrane adaptor protein LAB.
abstract: LAB (linker for activation of B cells), also known as NTAL (non-T cell activation linker), is a LAT (linker for activation of T cells)-like adaptor protein that is expressed in B, NK, and mast cells. Its role in lymphocytes has not been clearly demonstrated. Here, we showed that aged LAB-deficient (Lat2(-/-)) mice developed an autoimmune syndrome. Lat2(-/-) T cells were hyperactivated and produced more cytokines than Lat2(+/+) T cells. Even though LAB was absent in naive T cells, LAB could be detected in activated Lat2(+/+) T cells. LAT-mediated signaling events were enhanced in Lat2(-/-) T cells; however, they were suppressed in T cells that overexpressed LAB. Mice with the Lat2 gene conditionally deleted from T cells also developed the autoimmune syndrome like Lat2(-/-) mice. Together, these data demonstrated an important role of LAB in limiting autoimmune response and exposed a mechanism regulating T cell activation.
authors.affiliation: Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Minghua
authors.initials: M
authors.lastname: Zhu
authors.forename: Surapong
authors.initials: S
authors.lastname: Koonpaew
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.forename: Shudan
authors.initials: S
authors.lastname: Shen
authors.forename: Timothy
authors.initials: T
authors.lastname: Denning
authors.forename: Ivan
authors.initials: I
authors.lastname: Dzhagalov
authors.forename: Inmoo
authors.initials: I
authors.lastname: Rhee
authors.forename: Weiguo
authors.initials: W
authors.lastname: Zhang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000172:deficiency / Q000276:immunology*; D000367:Age Factors; D000818:Animals; D001327:Autoimmune Diseases / Q000209:etiology / Q000276:immunology; D015551:Autoimmunity; D005434:Flow Cytometry; D015870:Gene Expression; D015151:Immunoblotting; D008213:Lymphocyte Activation / Q000276:immunology*; D008565:Membrane Proteins / Q000172:deficiency / Q000276:immunology*; D051379:Mice; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D008565:Membrane Proteins