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Published in Science translational medicine - 05 Sep 2018

Clave E, Araujo IL, Alanio C, Patin E, Bergstedt J, Urrutia A, Lopez-Lastra S, Li Y, Charbit B, MacPherson CR, Hasan M, Melo-Lima BL, Douay C, Saut N, Germain M, Trégouët DA, Morange PE, Fontes M, Duffy D, Di Santo JP, Quintana-Murci L, Albert ML, Toubert A,

Link to Pubmed [PMID] – 30185651

Sci Transl Med 2018 Sep;10(457)

The thymus is the primary lymphoid organ where naïve T cells are generated; however, with the exception of age, the parameters that govern its function in healthy humans remain unknown. We characterized the variability of thymic function among 1000 age- and sex-stratified healthy adults of the Milieu Intérieur cohort, using quantification of T cell receptor excision circles (TRECs) in peripheral blood T cells as a surrogate marker of thymopoiesis. Age and sex were the only nonheritable factors identified that affect thymic function. TREC amounts decreased with age and were higher in women compared to men. In addition, a genome-wide association study revealed a common variant (rs2204985) within the T cell receptor locus, between the and gene segments, which associated with TREC amounts. Strikingly, transplantation of human hematopoietic stem cells with the rs2204985 GG genotype into immunodeficient mice led to thymopoiesis with higher TRECs, increased thymocyte counts, and a higher TCR repertoire diversity. Our population immunology approach revealed a genetic locus that influences thymopoiesis in healthy adults, with potentially broad implications in precision medicine.

https://www.ncbi.nlm.nih.gov/pubmed/30185651