I am excited to share the work that composed the majority of my PhD, now published in #CellMolImmunol
@natureportfolio Here is a small 🧶 (1/13)
https://www.nature.com/articles/s41423-023-01052-7
(2/13) We studied the glycome of human and murine thymocytes and asked whether a N-glycosylation blockade would affect murine T cell development and susceptibility to disease
(4/13) Ever since Peter Nowell discovered that a plant lectin could stimulate T cells in vitro, it has been clear that the glycome should play a major role on regulating T cell activity and function
https://aacrjournals.org/cancerres/article/20/4/462/474488/Phytohemagglutinin-An-Initiator-of-Mitosis-in
(6/13) In our work we show that the glycocalyx composition is dynamic across developing thymocytes, both in human and mice, using plant lectins
(7/13) In addition, we analyzed available scRNA-seq data from human and murine thymocytes and observed that key glycogenes’ expression levels displayed the same dynamic developmental features as the lectin binding levels
(8/13) Amazed by these glycome dynamics, we then generated Mgat1 conditional knockout mice, using a Rag1Cre line, having a blockade in the N-glycosylation pathway early in development
(9/13) These mice had severe developmental defects, when compared to their littermate controls
(10/13) Defects included impaired ß-selection, thymic Treg generation and altered TCRvß repertoires in CD8 SP thymocytes
(11/13) Finally, these mice showed spontaneous features of inflammation and were more susceptible to experimental inflammatory disease
(12/13) I am so glad to see this work published and would like to thank Salomé Pinho, my PhD advisor and captain of these scientific voyages
(5/13) In a seminal paper, the Demetriou´s lab showed that the degree of N-glycan branching of thymocytes tuned the affinity range for TCR-based selection
https://pubmed.ncbi.nlm.nih.gov/25263124/