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
(3/13) It has been known for decades that mature thymocytes possess some glycans that immature ones do not. However, research on the glycome of thymocytes and how it regulates developmental checkpoints has only received episodic, but seminal, attention
https://www.sciencedirect.com/science/article/pii/0008874976901039?via%3Dihub
(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
(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/
(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
(13/13) Also, I would like to thank members of the group our wonderful collaborators
(6/13) In our work we show that the glycocalyx composition is dynamic across developing thymocytes, both in human and mice, using plant lectins