Document Detail


Developmental regulation of Th17-cell capacity in human neonates.
MedLine Citation:
PMID:  22101893     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Human neonates are at significantly greater risk of serious infection than immunocompetent adults. In particular, very low birth weight infants in the neonatal intensive care nursery are at high risk of developing life-threatening bacterial and fungal infections. Recent studies have identified Th17 cells as critical mediators of immunity to bacterial and fungal infections at epithelial barriers. Little is known, however, about the ontogeny of Th17-cell responses in humans. The frequency of serious bacterial infections in preterm infants and the importance of Th17 cells in providing protection against such infections in animal studies prompted us to study Th17-cell development in human neonates. Naïve CD4(+) T cells from extremely preterm infants, term infants, and adults were assayed for their capacity to develop into Th17 effector cells. Surprisingly, Th17-cell capacity was inversely related to developmental age. Neonates expressed higher levels of IL-23R, RORγt, and STAT3 prior to activation and showed a significant Th17-cell bias after activation. In contrast, adult cells expressed more TBX21 with a corresponding Th1-cell bias. CD161 expression on Th17-cell precursors was also developmentally regulated. Our results suggest there is significant developmental regulation of CD4(+) effector lineages with a strong bias toward Th17-cell development early in life.
Authors:
Allison Black; Suniti Bhaumik; Richard L Kirkman; Casey T Weaver; David A Randolph
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-12-19
Journal Detail:
Title:  European journal of immunology     Volume:  42     ISSN:  1521-4141     ISO Abbreviation:  Eur. J. Immunol.     Publication Date:  2012 Feb 
Date Detail:
Created Date:  2012-01-23     Completed Date:  2012-03-21     Revised Date:  2013-06-27    
Medline Journal Info:
Nlm Unique ID:  1273201     Medline TA:  Eur J Immunol     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  311-9     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Affiliation:
Division of Neonatology, Department of Pediatrics, University of Alabama School of Medicine, Birmingham, AL 35249, USA.
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MeSH Terms
Descriptor/Qualifier:
Adult
Antigens, CD / genetics,  metabolism
Cell Separation
Cells, Cultured
Cytokines / metabolism*
Flow Cytometry
Gene Expression Regulation, Developmental* / immunology
Humans
Infant, Newborn
Nuclear Receptor Subfamily 1, Group F, Member 3 / genetics,  metabolism
Premature Birth / immunology*
Receptors, Interleukin / genetics,  metabolism
STAT3 Transcription Factor / genetics,  metabolism
Signal Transduction / immunology
T-Box Domain Proteins / genetics,  metabolism
Th1 Cells / immunology,  metabolism*,  pathology
Th1-Th2 Balance
Th17 Cells / immunology,  metabolism*,  pathology
Grant Support
ID/Acronym/Agency:
P01DK071176/DK/NIDDK NIH HHS; R00 HD056222/HD/NICHD NIH HHS; R00HD056222/HD/NICHD NIH HHS
Chemical
Reg. No./Substance:
0/Antigens, CD; 0/Cytokines; 0/IL23R protein, human; 0/Nuclear Receptor Subfamily 1, Group F, Member 3; 0/Receptors, Interleukin; 0/STAT3 Transcription Factor; 0/T-Box Domain Proteins; 0/T-box transcription factor TBX21
Comments/Corrections

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