Abstract

1. Following on our studies of the T-cell receptor repertoires of rare immune deficiency, we collaborated with Nan-Ping Weng's group to analyze the repertoires of normal CD4 and CD8 T-cells, finding a distinct pattern of TCR usage in CD4 vs. CD8 T-cells, and that unique CDR3 regions could actually be paired with multiple different variable region genes. The work was published in the Journal of Leukocyte Biology. 2. In collaboration with David Corry, Baylor College of Medicine, we found that long-acting beta adrenergic agonists (LABA)-- long used for asthma management, but known to have a number of adverse outcomes and effects, including worsening of asthma-- could alter T-cell phenotypes by enhancing STAT6 activation, which mirrored that seen in lung epithelial cells. These findings have significant implications for management with LABA, and for T-cell and Th2 biology. The findings were published in PLoS One.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIAAI001099-08
Application #
9354872
Study Section
Project Start
Project End
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Budget End
Support Year
8
Fiscal Year
2016
Total Cost
Indirect Cost

  Institution

Name
Niaid Extramural Activities
Department
Type
DUNS #
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  Publications

Mitson-Salazar, Alyssa; Yin, Yuzhi; Wansley, Daniel L et al. (2016) Hematopoietic prostaglandin D synthase defines a proeosinophilic pathogenic effector human T(H)2 cell subpopulation with enhanced function. J Allergy Clin Immunol 137:907-18.e9
Li, Hoi Ming; Hiroi, Toyoko; Zhang, Yongqing et al. (2016) TCR? repertoire of CD4+ and CD8+ T cells is distinct in richness, distribution, and CDR3 amino acid composition. J Leukoc Biol 99:505-13
Wan, Chi-Keung; Andraski, Allison B; Spolski, Rosanne et al. (2015) Opposing roles of STAT1 and STAT3 in IL-21 function in CD4+ T cells. Proc Natl Acad Sci U S A 112:9394-9
Knight, John M; Mak, Garbo; Shaw, Joanne et al. (2015) Long-Acting Beta Agonists Enhance Allergic Airway Disease. PLoS One 10:e0142212
Zhang, Yu; Yu, Xiaomin; Ichikawa, Mie et al. (2014) Autosomal recessive phosphoglucomutase 3 (PGM3) mutations link glycosylation defects to atopy, immune deficiency, autoimmunity, and neurocognitive impairment. J Allergy Clin Immunol 133:1400-9, 1409.e1-5
Yu, Xiaomin; Almeida, Jorge R; Darko, Sam et al. (2014) Human syndromes of immunodeficiency and dysregulation are characterized by distinct defects in T-cell receptor repertoire development. J Allergy Clin Immunol 133:1109-15
Barber, John S; Yokomizo, Lauren K; Sheikh, Virginia et al. (2013) Peptide library-based evaluation of T-cell receptor breadth detects defects in global and regulatory activation in human immunologic diseases. Proc Natl Acad Sci U S A 110:8164-9
Lawrence, Monica G; Barber, John S; Sokolic, Robert A et al. (2013) Elevated IgE and atopy in patients treated for early-onset ADA-SCID. J Allergy Clin Immunol 132:1444-6
Paul, William E; Milner, Joshua D; Grossman, Zvi (2013) Pathogen-sensing, regulatory T cells, and responsiveness-tuning collectively regulate foreign- and self-antigen mediated T-cell responses. Cold Spring Harb Symp Quant Biol 78:265-76
Hirahara, Kiyoshi; Poholek, Amanda; Vahedi, Golnaz et al. (2013) Mechanisms underlying helper T-cell plasticity: implications for immune-mediated disease. J Allergy Clin Immunol 131:1276-87

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