6 research outputs found
Rewiring of the TCR signalosome in natural intestinal Intraepithelial T lymphocytes drives non-deletional tolerance
Intraepithelial T lymphocytes (T-IEL) are a large population of cytotoxic T cells that protect the small intestinal epithelium against pathogens. Based on ontogeny, T-IEL can be categorized into two major subsets: induced and natural. Natural T-IEL are agonistically selected in the thymus on self-antigens before migrating directly to the small intestine. Despite having self-reactive T cell antigen receptors (TCR), natural T-IEL are maintained in a tolerized state in the gut by unknown mechanisms. We therefore investigated TCR signaling in T-IEL using multiplexed fluorescent cell barcoding, phosphoproteomics and TCR signaling reporter mouse models, which revealed that TCR signaling is intrinsically suppressed in natural, but not induced, T-IEL. Unexpectedly, we discover that this cell intrinsic suppression was mediated through altered TCR signalosome components. Specifically, downregulation of the key signaling adaptor, Linker for activation of T cells (LAT) during thymic selection is a vital checkpoint for the development and tolerization of natural IELs. Thus, TCR signaling is rewired in self-reactive natural T-IEL to promote tolerance and prevent inappropriate inflammation in the gut.One sentence summary Self-reactive natural intestinal intraepithelial T lymphocytes are developmentally tolerized by rewiring the T cell antigen receptor signaling pathway through the downregulation of the adaptor protein, LAT
Rewiring of the TCR signalosome in natural intestinal Intraepithelial T lymphocytes drives non-deletional tolerance
Intraepithelial T lymphocytes (T-IEL) are a large population of cytotoxic T cells that protect the small intestinal epithelium against pathogens. Based on ontogeny, T-IEL can be categorized into two major subsets: induced and natural. Natural T-IEL are agonistically selected in the thymus on self-antigens before migrating directly to the small intestine. Despite having self-reactive T cell antigen receptors (TCR), natural T-IEL are maintained in a tolerized state in the gut by unknown mechanisms. We therefore investigated TCR signaling in T-IEL using multiplexed fluorescent cell barcoding, phosphoproteomics and TCR signaling reporter mouse models, which revealed that TCR signaling is intrinsically suppressed in natural, but not induced, T-IEL. Unexpectedly, we discover that this cell intrinsic suppression was mediated through altered TCR signalosome components. Specifically, downregulation of the key signaling adaptor, Linker for activation of T cells (LAT) during thymic selection is a vital checkpoint for the development and tolerization of natural IELs. Thus, TCR signaling is rewired in self-reactive natural T-IEL to promote tolerance and prevent inappropriate inflammation in the gut.One sentence summary Self-reactive natural intestinal intraepithelial T lymphocytes are developmentally tolerized by rewiring the T cell antigen receptor signaling pathway through the downregulation of the adaptor protein, LAT
Investigations of Optical Coherence Properties in an Erbium-doped Silicate Fiber for Quantum State Storage
We studied optical coherence properties of the 1.53 m telecommunication
transition in an Er-doped silicate optical fiber through spectral
holeburning and photon echoes. We find decoherence times of up to 3.8 s at
a magnetic field of 2.2 Tesla and a temperature of 150 mK. A strong
magnetic-field dependent optical dephasing was observed and is believed to
arise from an interaction between the electronic Er spin and the
magnetic moment of tunneling modes in the glass. Furthermore, we observed
fine-structure in the Erbium holeburning spectrum originating from
superhyperfine interaction with Al host nuclei. Our results show that
Er-doped silicate fibers are promising material candidates for quantum
state storage
Rewiring of the TCR signalosome in natural intestinal Intraepithelial T lymphocytes drives non-deletional tolerance
Intraepithelial T lymphocytes (T-IEL) are a large population of cytotoxic T cells that protect the small intestinal epithelium against pathogens. Based on ontogeny, T-IEL can be categorized into two major subsets: induced and natural. Natural T-IEL are agonistically selected in the thymus on self-antigens before migrating directly to the small intestine. Despite having self-reactive T cell antigen receptors (TCR), natural T-IEL are maintained in a tolerized state in the gut by unknown mechanisms. We therefore investigated TCR signaling in T-IEL using multiplexed fluorescent cell barcoding, phosphoproteomics and TCR signaling reporter mouse models, which revealed that TCR signaling is intrinsically suppressed in natural, but not induced, T-IEL. Unexpectedly, we discover that this cell intrinsic suppression was mediated through altered TCR signalosome components. Specifically, downregulation of the key signaling adaptor, Linker for activation of T cells (LAT) during thymic selection is a vital checkpoint for the development and tolerization of natural IELs. Thus, TCR signaling is rewired in self-reactive natural T-IEL to promote tolerance and prevent inappropriate inflammation in the gut