Neonatal T Helper 17 Responses Are Skewed Towards an Immunoregulatory Interleukin-22 Phenotype.

Autor:	Razzaghian HR; BC Children's Hospital Research Institute, University of British Columbia, Vancouver, BC, Canada.; Department of Pediatrics, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada., Sharafian Z; BC Children's Hospital Research Institute, University of British Columbia, Vancouver, BC, Canada.; Department of Pediatrics, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada.; Experimental Medicine Program, Department of Medicine, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada., Sharma AA; BC Children's Hospital Research Institute, University of British Columbia, Vancouver, BC, Canada.; Department of Pediatrics, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada.; Experimental Medicine Program, Department of Medicine, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada.; Department of Pathology & Laboratory Medicine, School of Medicine, Emory University, Atlanta, GA, United States., Boyce GK; BC Children's Hospital Research Institute, University of British Columbia, Vancouver, BC, Canada.; Department of Pediatrics, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada.; Experimental Medicine Program, Department of Medicine, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada., Lee K; BC Children's Hospital Research Institute, University of British Columbia, Vancouver, BC, Canada.; Department of Pediatrics, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada., Da Silva R; BC Children's Hospital Research Institute, University of British Columbia, Vancouver, BC, Canada., Orban PC; BC Children's Hospital Research Institute, University of British Columbia, Vancouver, BC, Canada.; Department of Surgery, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada., Sekaly RP; Department of Pathology & Laboratory Medicine, School of Medicine, Emory University, Atlanta, GA, United States., Ross CJ; BC Children's Hospital Research Institute, University of British Columbia, Vancouver, BC, Canada.; Faculty of Pharmaceutical Sciences, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada., Lavoie PM; BC Children's Hospital Research Institute, University of British Columbia, Vancouver, BC, Canada.; Department of Pediatrics, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada.; Experimental Medicine Program, Department of Medicine, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2021 May 03; Vol. 12, pp. 655027. Date of Electronic Publication: 2021 May 03 (Print Publication: 2021).
DOI:	10.3389/fimmu.2021.655027
Abstrakt:	Newborns are frequently affected by mucocutaneous candidiasis. Th17 cells essentially limit mucosal invasion by commensal Candida spp. Here, we sought to understand the molecular basis for the developmental lack of Th17 cell responses in circulating blood neonatal T cells. Naive cord blood CD4 T cells stimulated in Th17-differentiating conditions inherently produced high levels of the interleukin-22 immunoregulatory cytokine, particularly in the presence of neonatal antigen-presenting cells. A genome-wide transcriptome analysis comparing neonatal and adult naïve CD4 T cells ex vivo revealed major developmental differences in gene networks regulating Small Drosophila Mothers Against Decapentaplegic (SMAD) and Signal Transducer and Activator of Transcription 3 (STAT3) signaling. These changes were functionally validated by experiments showing that the requirement for TGF-β in human Th17 cell differentiation is age-dependent. Moreover, STAT3 activity was profoundly diminished while overexpression of the STAT3 gene restored Th17 cell differentiation capacity in neonatal T cells. These data reveal that Th17 cell responses are developmentally regulated at the gene expression level in human neonates. These developmental changes may protect newborns against pathological Th17 cell responses, at the same time increasing their susceptibility to mucocutaneous candidiasis. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2021 Razzaghian, Sharafian, Sharma, Boyce, Lee, Da Silva, Orban, Sekaly, Ross and Lavoie.)
Databáze:	MEDLINE
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