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Developmental regulation of Th17-cell capacity in human neonates

Allison Black1, Suniti Bhaumik, Richard L Kirkman

  • 1Division of Neonatology, Department of Pediatrics, University of Alabama School of Medicine, Birmingham, AL 35249, USA.

European Journal of Immunology
|November 22, 2011
PubMed

Insights

Neonates show a strong bias toward developing Th17 cells, crucial for fighting infections, unlike adults who favor Th1 cells. This finding reveals developmental regulation of immune responses in early life.

Area of Science:

  • Immunology
  • Developmental Biology
  • Neonatal Medicine

Background:

  • Human neonates, especially preterm infants, face a higher risk of severe infections.
  • Th17 cells are vital for immunity against bacterial and fungal pathogens at epithelial barriers.
  • The developmental trajectory of human Th17 cell responses remains largely uncharacterized.

Purpose of the Study:

  • To investigate the ontogeny of T helper 17 (Th17) cell development in human neonates.
  • To compare Th17 cell differentiation capacity in neonates versus adults.
  • To identify key molecular factors regulating Th17 cell development in early life.

Main Methods:

  • Assaying the capacity of naive CD4(+) T cells from extremely preterm infants, term infants, and adults to differentiate into Th17 effector cells.
  • Measuring the expression levels of key Th17-associated genes and proteins (IL-23R, RORγt, STAT3, TBX21, CD161) before and after activation.
  • Analyzing the developmental regulation of CD4(+) T cell effector lineages.

Main Results:

  • Th17 cell differentiation capacity was inversely correlated with developmental age, being higher in neonates than adults.
  • Neonatal T cells exhibited higher pre-activation expression of IL-23R, RORγt, and STAT3, leading to a Th17-cell bias post-activation.
  • Adult T cells showed a preference for Th1 cell development, indicated by higher TBX21 expression.
  • CD161 expression on Th17 cell precursors demonstrated developmental regulation.

Conclusions:

  • Human T helper cell differentiation is developmentally regulated, with a significant bias towards Th17 cell development in early life.
  • These findings highlight a unique immunological profile in neonates that may influence their susceptibility and response to infections.
  • Understanding this developmental bias is crucial for managing infections in vulnerable infant populations.

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