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Presumption of guilt for T cells in type 1 diabetes: lead culprits or partners in crime depending on age of onset? – published online 21/10/2020

Carre GA

Alexia Carré, Sarah J. Richardson, Etienne Larger, Roberto Mallone

It is increasingly recognised that autoimmune type 1 diabetes is a tale of two main characters that both play a role in disease pathogenesis: the T cell and the beta cell. On one hand, the presumption of innocence traditionally granted to beta cells requires revision, as recently reviewed in Diabetologia by Mallone and Eizirik ( . On the other hand, the presumption of guilt that T cells are often charged with may also need to be reconsidered. In this review, Carré et al ( evaluate genetic, histopathological, functional and clinical evidence to argue that T cells may behave as ‘lead culprits’ or ‘partners in crime’ in type 1 diabetes, depending on specific disease endotypes, mostly related to age. Increasing evidence points to the existence of a younger-onset endotype with more aggressive autoimmunity and an older-onset endotype with more vulnerable beta cells. Current challenges and opportunities for dissecting this disease heterogeneity are discussed. The figures from this review are available as a downloadable slideset.

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