Negative regulation of T cell activation and autoimmunity by the transmembrane adaptor protein LAB.
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.
Zhu
Minghua
M
Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA.
Koonpaew
Surapong
S
Liu
Yan
Y
Shen
Shudan
S
Denning
Timothy
T
Dzhagalov
Ivan
I
Rhee
Inmoo
I
Zhang
Weiguo
W
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*
D048868:Adaptor Proteins, Signal Transducing; D008565:Membrane Proteins