Institution
University of Alabama at Birmingham
Education•Birmingham, Alabama, United States•
About: University of Alabama at Birmingham is a education organization based out in Birmingham, Alabama, United States. It is known for research contribution in the topics: Population & Medicine. The organization has 38523 authors who have published 86775 publications receiving 3930642 citations. The organization is also known as: UAB & The University of Alabama at Birmingham.
Topics: Population, Medicine, Cancer, Poison control, Health care
Papers published on a yearly basis
Papers
More filters
••
TL;DR: The search for the phylogenetic roots of adaptive immunity in the lamprey has instead identified a new type of variable lymphocyte receptors (VLRs) composed of highly diverse leucine-rich repeats (LRR) sandwiched between amino- and carboxy-terminal LRRs.
Abstract: Although jawless vertebrates are apparently capable of adaptive immune responses, they have not been found to possess the recombinatorial antigen receptors shared by all jawed vertebrates. Our search for the phylogenetic roots of adaptive immunity in the lamprey has instead identified a new type of variable lymphocyte receptors (VLRs) composed of highly diverse leucine-rich repeats (LRR) sandwiched between amino- and carboxy-terminal LRRs. An invariant stalk region tethers the VLRs to the cell surface by means of a glycosyl-phosphatidyl-inositol anchor. To generate rearranged VLR genes of the diversity necessary for an anticipatory immune system, the single lamprey VLR locus contains a large bank of diverse LRR cassettes, available for insertion into an incomplete germline VLR gene. Individual lymphocytes express a uniquely rearranged VLR gene in monoallelic fashion. Different evolutionary strategies were thus used to generate highly diverse lymphocyte receptors through rearrangement of LRR modules in agnathans (jawless fish) and of immunoglobulin gene segments in gnathostomes (jawed vertebrates).
634 citations
••
The American College of Financial Services1, Icahn School of Medicine at Mount Sinai2, Wayne State University3, Emory University4, Cleveland Clinic5, University of California, San Diego6, Ochsner Medical Center7, Louisiana State University8, University of Tennessee Health Science Center9, University of Texas at Dallas10, American Association of Clinical Endocrinologists11, Harvard University12, Baylor College of Medicine13, University of Alabama at Birmingham14, Veterans Health Administration15, University of Washington16, Mayo Clinic17, University of Miami18, University of California, Santa Barbara19, SUNY Downstate Medical Center20, University of Arizona21, Washington University in St. Louis22, University of Southern California23, University of California, Los Angeles24, University of California, Irvine25, Eastern Virginia Medical School26, Cornell University27
TL;DR: These guidelines are a working document that reflects the state of the field at the time of publication and any decision by practitioners to apply these guidelines must be made in light of local resources and individual patient circumstances.
634 citations
••
TL;DR: New candidate genes for serum urate concentration highlight the importance of metabolic control of urate production and excretion, which may have implications for the treatment and prevention of gout.
Abstract: Elevated serum urate concentrations can cause gout, a prevalent and painful inflammatory arthritis. By combining data from >140,000 individuals of European ancestry within the Global Urate Genetics Consortium (GUGC), we identified and replicated 28 genome-wide significant loci in association with serum urate concentrations (18 new regions in or near TRIM46, INHBB, SFMBT1, TMEM171, VEGFA, BAZ1B, PRKAG2, STC1, HNF4G, A1CF, ATXN2, UBE2Q2, IGF1R, NFAT5, MAF, HLF, ACVR1B-ACVRL1 and B3GNT4). Associations for many of the loci were of similar magnitude in individuals of non-European ancestry. We further characterized these loci for associations with gout, transcript expression and the fractional excretion of urate. Network analyses implicate the inhibins-activins signaling pathways and glucose metabolism in systemic urate control. New candidate genes for serum urate concentration highlight the importance of metabolic control of urate production and excretion, which may have implications for the treatment and prevention of gout.
633 citations
••
TL;DR: Two new fate-mapping mouse models are used to show that CD4+ T cells that formerly expressed IL-17A go on to acquire an anti-inflammatory phenotype and suggest that Th17 cell instability and plasticity is a therapeutic opportunity for inflammatory diseases.
Abstract: Inflammation is a beneficial host response to infection but can contribute to inflammatory disease if unregulated The Th17 lineage of T helper (Th) cells can cause severe human inflammatory diseases These cells exhibit both instability (they can cease to express their signature cytokine, IL-17A) and plasticity (they can start expressing cytokines typical of other lineages) upon in vitro re-stimulation However, technical limitations have prevented the transcriptional profiling of pre- and post-conversion Th17 cells ex vivo during immune responses Thus, it is unknown whether Th17 cell plasticity merely reflects change in expression of a few cytokines, or if Th17 cells physiologically undergo global genetic reprogramming driving their conversion from one T helper cell type to another, a process known as transdifferentiation Furthermore, although Th17 cell instability/plasticity has been associated with pathogenicity, it is unknown whether this could present a therapeutic opportunity, whereby formerly pathogenic Th17 cells could adopt an anti-inflammatory fate Here we used two new fate-mapping mouse models to track Th17 cells during immune responses to show that CD4(+) T cells that formerly expressed IL-17A go on to acquire an anti-inflammatory phenotype The transdifferentiation of Th17 into regulatory T cells was illustrated by a change in their signature transcriptional profile and the acquisition of potent regulatory capacity Comparisons of the transcriptional profiles of pre- and post-conversion Th17 cells also revealed a role for canonical TGF-β signalling and consequently for the aryl hydrocarbon receptor (AhR) in conversion Thus, Th17 cells transdifferentiate into regulatory cells, and contribute to the resolution of inflammation Our data suggest that Th17 cell instability and plasticity is a therapeutic opportunity for inflammatory diseases
633 citations
••
TL;DR: It is identified that ILCs maintain intestinal homeostasis through MHCII-dependent interactions with CD4+ T cells that limit pathological adaptive immune cell responses to commensal bacteria.
Abstract: Innate lymphoid cells (ILCs) are a recently characterized family of immune cells that have critical roles in cytokine-mediated regulation of intestinal epithelial cell barrier integrity. Alterations in ILC responses are associated with multiple chronic human diseases, including inflammatory bowel disease, implicating a role for ILCs in disease pathogenesis. Owing to an inability to target ILCs selectively, experimental studies assessing ILC function have predominantly used mice lacking adaptive immune cells. However, in lymphocyte-sufficient hosts ILCs are vastly outnumbered by CD4(+) T cells, which express similar profiles of effector cytokines. Therefore, the function of ILCs in the presence of adaptive immunity and their potential to influence adaptive immune cell responses remain unknown. To test this, we used genetic or antibody-mediated depletion strategies to target murine ILCs in the presence of an adaptive immune system. We show that loss of retinoic-acid-receptor-related orphan receptor-γt-positive (RORγt(+)) ILCs was associated with dysregulated adaptive immune cell responses against commensal bacteria and low-grade systemic inflammation. Remarkably, ILC-mediated regulation of adaptive immune cells occurred independently of interleukin (IL)-17A, IL-22 or IL-23. Genome-wide transcriptional profiling and functional analyses revealed that RORγt(+) ILCs express major histocompatibility complex class II (MHCII) and can process and present antigen. However, rather than inducing T-cell proliferation, ILCs acted to limit commensal bacteria-specific CD4(+) T-cell responses. Consistent with this, selective deletion of MHCII in murine RORγt(+) ILCs resulted in dysregulated commensal bacteria-dependent CD4(+) T-cell responses that promoted spontaneous intestinal inflammation. These data identify that ILCs maintain intestinal homeostasis through MHCII-dependent interactions with CD4(+) T cells that limit pathological adaptive immune cell responses to commensal bacteria.
633 citations
Authors
Showing all 38940 results
Name | H-index | Papers | Citations |
---|---|---|---|
Rudolf Jaenisch | 206 | 606 | 178436 |
Joel Schwartz | 183 | 1149 | 109985 |
Tadamitsu Kishimoto | 181 | 1067 | 130860 |
Jasvinder A. Singh | 176 | 2382 | 223370 |
Gregg L. Semenza | 168 | 502 | 130316 |
David R. Jacobs | 165 | 1262 | 113892 |
Hua Zhang | 163 | 1503 | 116769 |
David R. Holmes | 161 | 1624 | 114187 |
David Cella | 156 | 1258 | 106402 |
Elaine S. Jaffe | 156 | 828 | 112412 |
Michael A. Matthay | 151 | 998 | 98687 |
Lawrence Corey | 146 | 773 | 78105 |
Barton F. Haynes | 144 | 911 | 79014 |
Douglas D. Richman | 142 | 633 | 82806 |
Kjell Fuxe | 142 | 1479 | 89846 |