NDLI: Thymic involution perturbs negative selection leading to autoreactive T cells that induce chronic inflammation.

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Invariant NKT cells require autophagy to coordinate proliferation and survival signals during differentiation.

The distal upstream promoter in Ly49 genes, Pro1, is active in mature NK cells and T cells, does not require TATA boxes, and displays enhancer activity.

DCIR maintains bone homeostasis by regulating IFN-Î³ production in T cells.

IL-33 receptor ST2 amplifies the expansion of NK cells and enhances host defense during mouse cytomegalovirus infection.

PD-1 upregulated on regulatory T cells during chronic virus infection enhances the suppression of CD8+ T cell immune response via the interaction with PD-L1 expressed on CD8+ T cells.

A novel lung explant model for the ex vivo study of efficacy and mechanisms of anti-influenza drugs.

Transcription factors STAT6 and KLF4 implement macrophage polarization via the dual catalytic powers of MCPIP.

Nanotubes connect CD4+ T cells to airway smooth muscle cells: novel mechanism of T cell survival.

Laser-assisted intradermal delivery of adjuvant-free vaccines targeting XCR1+ dendritic cells induces potent antitumoral responses.

De novo-developed antibodies to donor MHC antigens lead to dysregulation of microRNAs and induction of MHC class II.

Diverse inflammatory cytokines induce selectin ligand expression on murine CD4 T cells via p38 MAPK.

A population response analysis approach to assign class II HLA-epitope restrictions.

Identification of a nuclear export sequence in the MHC CIITA.

Crucial roles of TNFAIP8 protein in regulating apoptosis and Listeria infection.

Exacerbated experimental colitis in TNFAIP8-deficient mice.

Species-specific differences in the expression and regulation of 4ß7 integrin in various nonhuman primates.

Regulation of neutrophilic inflammation by proteinase-activated receptor 1 during bacterial pulmonary infection.

Determinants of gliadin-specific T cell selection in celiac disease.

De novo-induced self-antigen-specific Foxp3+ regulatory T cells impair the accumulation of inflammatory dendritic cells in draining lymph nodes.

Batf2/Irf1 induces inflammatory responses in classically activated macrophages, lipopolysaccharides, and mycobacterial infection.

Generation of TCR-engineered T cells and their use to control the performance of T cell assays.

Thymic involution perturbs negative selection leading to autoreactive T cells that induce chronic inflammation.

Genetic variation in SP-A2 leads to differential binding to Mycoplasma pneumoniae membranes and regulation of host responses.

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Neonatal exposure to pneumococcal phosphorylcholine modulates the development of house dust mite allergy during adult life.

Quantitative profiling of immune repertoires for minor lymphocyte counts using unique molecular identifiers.

CXCL14 displays antimicrobial activity against respiratory tract bacteria and contributes to clearance of Streptococcus pneumoniae pulmonary infection.

Pyruvate dehydrogenase kinase 1 participates in macrophage polarization via regulating glucose metabolism.

GIMAP GTPase family genes: potential modifiers in autoimmune diabetes, asthma, and allergy.

Candida albicans stimulates IL-23 release by human dendritic cells and downstream IL-17 secretion by VÎ´1 T cells.

IRF-1 promotes liver transplant ischemia/reperfusion injury via hepatocyte IL-15/IL-15R production.

Diverse antibody genetic and recognition properties revealed following HIV-1 envelope glycoprotein immunization.

Identification of the inflammasome Nlrp1b as the candidate gene conferring diabetes risk at the Idd4.1 locus in the nonobese diabetic mouse.

Immune tolerance induction with multiepitope peptide derived from citrullinated autoantigens attenuates arthritis manifestations in adjuvant arthritis rats.

Glucocorticoid-induced leucine zipper: a critical factor in macrophage endotoxin tolerance.

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CD81 controls immunity to Listeria infection through rac-dependent inhibition of proinflammatory mediator release and activation of cytotoxic T cells.

The Notch signaling pathway controls short-lived effector CD8+ T cell differentiation but is dispensable for memory generation.

Characterization of a human platelet antigen-1a-specific monoclonal antibody derived from a B cell from a woman alloimmunized in pregnancy.

Vinpocetine inhibits Streptococcus pneumoniae-induced upregulation of mucin MUC5AC expression via induction of MKP-1 phosphatase in the pathogenesis of otitis media.

Cutting edge: c-Kit signaling differentially regulates type 2 innate lymphoid cell accumulation and susceptibility to central nervous system demyelination in male and female SJL mice.

A CD153+CD4+ T follicular cell population with cell-senescence features plays a crucial role in lupus pathogenesis via osteopontin production.

Programmed death-1 controls T cell survival by regulating oxidative $metabolism^{}$

Thymic low affinity/avidity interaction selects natural Th1 cells.

Cryptococcal heat shock protein 70 homolog Ssa1 contributes to pulmonary expansion of Cryptococcus neoformans during the afferent phase of the immune response by promoting macrophage M2 polarization.

CD155 (PVR/Necl5) mediates a costimulatory signal in CD4+ T cells and regulates allergic inflammation.

Poly(inosinic-cytidylic) acid-triggered exacerbation of experimental asthma depends on IL-17A produced by NK cells.

The frequency of naive and early-activated hapten-specific B cell subsets dictates the efficacy of a therapeutic vaccine against prescription opioid abuse.

Cutting edge: Role of osteopontin and integrin v in T cell-mediated anti-inflammatory responses in endotoxemia.

Concordance of Increased B1 Cell Subset and Lupus Phenotypes in Mouse and Human Dependent on BLK Expression Levels

Analysis of celiac disease autoreactive gut plasma cells and their corresponding memory compartment in peripheral blood using high-throughput sequencing.

Genetic vaccines to potentiate the effective CD103+ dendritic cell-mediated cross-priming of antitumor immunity.

Involvement of the HCK and FGR src-family kinases in FCRL4-mediated immune regulation.

TLR2 stimulation regulates the balance between regulatory T cell and Th17 function: a novel mechanism of reduced regulatory T cell function in multiple sclerosis.

A synthetic M protein peptide synergizes with a CXC chemokine protease to induce vaccine-mediated protection against virulent streptococcal pyoderma and bacteremia.

Haploinsufficiency for Stard7 is associated with enhanced allergic responses in lung and skin.

Altered distribution and increased IL-17 production by mucosal-associated invariant T cells in adult and childhood obesity.

Amino acid metabolism inhibits antibody-driven kidney injury by inducing autophagy.

Platelet-activating factor receptor contributes to antileishmanial function of miltefosine.

J. Donald Capra, M.D. (1937-2015).

Nouvelle cuisine: platelets served with inflammation.

Intestinal fucose as a mediator of host-microbe symbiosis.

Retraction: Pregnancy-associated exosomes and their modulation of T cell signaling.

Correction: Viral MHC class I-like molecule allows evasion of NK cell effector responses in vivo.

Correction: Extracellular vesicles derived from gram-negative bacteria, such as Escherichia coli, induce emphysema mainly via IL-17A-mediated neutrophilic inflammation.

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Thymic involution perturbs negative selection leading to autoreactive T cells that induce chronic inflammation.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Coder, Brandon D. Ruan, Linhui Wang, Hongjun Su, Dong-Ming
Description	Author Affiliation: Coder BD ( Department of Cell Biology and Immunology, University of North Texas Health Science Center at Fort Worth, Fort Worth, TX 76107.); Wang H ( Department of Cell Biology and Immunology, University of North Texas Health Science Center at Fort Worth, Fort Worth, TX 76107.); Ruan L ( Department of Cell Biology and Immunology, University of North Texas Health Science Center at Fort Worth, Fort Worth, TX 76107.); Su DM ( Department of Cell Biology and Immunology, University of North Texas Health Science Center at Fort Worth, Fort Worth, TX 76107 dong-ming.su@unthsc.edu.)
Abstract	Thymic involution and the subsequent amplified release of autoreactive T cells increase the susceptibility toward developing autoimmunity, but whether they induce chronic inflammation with advanced age remains unclear. The presence of chronic low-level proinflammatory factors in elderly individuals (termed inflammaging) is a significant risk factor for morbidity and mortality in virtually every chronic age-related disease. To determine how thymic involution leads to the persistent release and activation of autoreactive T cells capable of inducing inflammaging, we used a Foxn1 conditional knockout mouse model that induces accelerated thymic involution while maintaining a young periphery. We found that thymic involution leads to T cell activation shortly after thymic egress, which is accompanied by a chronic inflammatory phenotype consisting of cellular infiltration into non-lymphoid tissues, increased TNF- production, and elevated serum IL-6. Autoreactive T cell clones were detected in the periphery of Foxn1 conditional knockout mice. A failure of negative selection, facilitated by decreased expression of Aire rather than impaired regulatory T cell generation, led to autoreactive T cell generation. Furthermore, the young environment can reverse age-related regulatory T cell accumulation in naturally aged mice, but not inflammatory infiltration. Taken together, these findings identify thymic involution and the persistent activation of autoreactive T cells as a contributing source of chronic inflammation (inflammaging).
ISSN	00221767
e-ISSN	15506606
DOI	10.4049/jimmunol.1500082
Journal	The Journal of Immunology
Issue Number	12
Volume Number	194
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2015-06-15
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Autoimmunity Clonal Selection, Antigen-mediated Inflammation Immunology T-lymphocyte Subsets Thymus Gland Animals Cellular Microenvironment Chronic Disease Clonal Deletion Genetics Disease Models, Animal Forkhead Transcription Factors Gene Knockdown Techniques Immunophenotyping Metabolism Lymphocyte Activation Mice Mice, Knockout Phenotype Thymocytes Cytology Research Support, N.i.h., Extramural Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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