Thymic output in human newborns is shaped by environmental exposures and a common TCRD genetic variant

Naïve T cell output from the thymus varies across the human lifespan and is a key determinant of health, differing between individuals by age, sex, and genetics. How thymic output is dynamically regulated early in life in response to initial microbial colonization remains unclear. We report longitudinal thymic output dynamics, measured as T cell receptor excision circles (TRECs), in 136 newborns from Stockholm, Sweden. Thymic output increases after birth following initial microbial colonization, peaking at 3–4 mo. Peak height correlates with plasma levels of RANKL and lymphotoxin-α and with a common genetic variant in the TCRD locus previously linked to adult thymopoiesis. B cell lymphopoiesis measured by KRECs reveals divergent dynamics between B and T cell branches of the adaptive immune system in early life. Findings are corroborated by thymic tissue analyses, in which local RANKL secretion correlates with medullary, but not cortical, epithelial cell numbers. These results illuminate the establishment of healthy immune–microbe interactions in early human life.

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Publication Details

Journal
Journal of Human Immunity
Published
2026-03-31
DOI
https://doi.org/10.70962/jhi.20260003
Primary Topic
T-cell and B-cell Immunology
Type
article
Field-Weighted Citation Impact
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article

Thymic output in human newborns is shaped by environmental exposures and a common TCRD genetic variant

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Journal of Human Immunity
T-cell and B-cell Immunology
article

Thymic output in human newborns is shaped by environmental exposures and a common TCRD genetic variant

Antonio Rausell, Magali Irla, Anna Karin Bernhardsson, Nadine Cerf–Bensussan, Lluís Quintana‐Murci, M. Ménager, Frédérique Michel, Emmanuel Clave, Jost Enninga, Rose Anne Kenny, Gunilla Karlsson Hedestam, Pierre Bruhns, Frédéric Tangy, Hugues Aschard, Tadepally Lakshmikanth, Ewa Henckel, Margarita Ivanchenko, Hugo Barcenilla, Serge Herçberg, Lars Rogge, Ziyang Tan, Jaromír Mikeš, Olivier Schwartz, Anette Johnsson, Benno Schwikowski, Marie‐Noëlle Ungeheuer, Hugo Mouquet, Ludovic Deriano, Camille Kergaravat, Christian Pou, Agata Cieślak, Petter Brodin, Marie‐Agnès Dillies, Jonathan Desponds, Andrés Alcover, D Duffy, A Gossage James, Mathilde Touvier, Magnus Fontes, Erika Negrini, Olivier Lantz, Etienne Patin, James Di Santo, Christophe Zimmer, Cliona O'Farrelly, Milena Hasan, Gérard Eberl, Christophe D'Enfert, Matthew L. Albert, Jacques Fellay, Spencer Shorte, Frédéric Rieux-Laucat, Vahid Asnafi, Anavaj Sakuntabhai, Ana Cumano, Nollaig Bourke, Ivo Gomperts-Boneca, Molly A. Ingersoll, Laurent Abel, Antoine Toubert, Laura Gonzalez, Yang Chen, Philippe Bousso
article en

Abstract

Naïve T cell output from the thymus varies across the human lifespan and is a key determinant of health, differing between individuals by age, sex, and genetics. How thymic output is dynamically regulated early in life in response to initial microbial colonization remains unclear. We report longitudinal thymic output dynamics, measured as T cell receptor excision circles (TRECs), in 136 newborns from Stockholm, Sweden. Thymic output increases after birth following initial microbial colonization, peaking at 3–4 mo. Peak height correlates with plasma levels of RANKL and lymphotoxin-α and with a common genetic variant in the TCRD locus previously linked to adult thymopoiesis. B cell lymphopoiesis measured by KRECs reveals divergent dynamics between B and T cell branches of the adaptive immune system in early life. Findings are corroborated by thymic tissue analyses, in which local RANKL secretion correlates with medullary, but not cortical, epithelial cell numbers. These results illuminate the establishment of healthy immune–microbe interactions in early human life.

Journal of Human ImmunityVol. 2(4)
Hôpital Necker-Enfants Malades (FR), Centre National de la Recherche Scientifique (FR), Inserm (FR), Institut Pasteur (FR), Université Paris Cité (FR), Hammersmith Hospital (GB), Karolinska Institutet (SE), Institut Necker Enfants Malades (FR), Sorbonne Paris Cité (FR), Assistance Publique – Hôpitaux de Paris (FR), Evolutionary Genomics (United States) (US), Laboratoire Vision Action Cognition (FR), Institut Cochin (FR), Centre d’Immunologie de Marseille-Luminy (FR), Hôpital Saint-Louis (FR), MRC London Institute of Medical Sciences (GB), Imperial College London (GB)
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T-cell and B-cell Immunology
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