Neonatal Treg and Research Motivations
Date: 10 March 2024
Author: Masahiro Ono
Recently I was reflecting on my research journey over the past two decades, its challenges and achievements. Today, I want to highlight a crucial factor that guided my research direction and sparked my initial motivation to develop Tocky.
Launching my PhD at Sakaguchi lab in 2002, I focused on GITR as a potentially useful Treg marker (note this was pre-Foxp3 era). I aimed to replicate early Treg experiments, including the milestone paper Asano et al., J Exp Med 1996 from the Sakaguchi group.
Asanot et al. claimed that CD25+ T cells do not appear before day 3 post-birth, which assertion was pivotal as it 'proved' that 'depletion of Tregs' by day 3 thymectomy caused autoimmunity.
I obtained a disturbing finding in 2003 (my second year in PhD): substantial numbers of Tregs existed in the neonatal spleen and thymus as early as day 1 after birth. This finding starkly contradicted the key claim of the Treg milestone paper by Asano et al., 1996.
This finding was not isolated—Dujardin et al 2004 from the Bandeira group presented very similar data to what I had discovered.
At that time, I believed that the Treg theory, which relied heavily on the findings of Asano et al 1996, would soon be revised. Unfortunately, that has not happened.
Many textbooks and reviews have echoed the findings of Asano et al, despite the evidence to the contrary regarding neonatal Treg dynamics. More recently, a milestone article on Treg by Svoboda in Nature (2022) still references the outdated notion as below.
This experience led me to scrutinize widely accepted papers and theories in the Treg field critically, convincing me that the Treg theories and concepts themselves needed substantial revision.
This realization prompted my move from Japan to the UK in 2009 to extend my research and develop new tools to investigate Treg. This endevour resulted in the development of the multidimensional method Canonical Correspondence Analysis (CCA) in genomics and Tocky.
