Extended Data Fig. 6: Mechanisms of ectopic lymphoid structure formation in salivary glands. | Nature Metabolism

Extended Data Fig. 6: Mechanisms of ectopic lymphoid structure formation in salivary glands.

From: Lactate signalling leads to aggregation of immune-inflammatory hotspots and SLC5A12 blockade promotes their resolution

Extended Data Fig. 6

The figure illustrates the proposed impact of lactate accumulation on T cell activation and the development of ectopic lymphoid structures in SjD SGs. (Left panel) Activated stromal cells, such as ductal epithelial cells, and infiltrating immune cells increase glycolysis, leading to lactate production and release into the microenvironment. CD4+ T cells uptake lactate via the SLC5A12 transporter. Lactate stimulates IL21 production by Tfh and Tph cells, driving B-cell activation and differentiation. (Right panel) Within the ectopic lymphoid structure, B cells organize into follicles supported by follicular dendritic cells (FDCs). Tfh cells provide help to B cells, leading to the production of autoantibodies and the generation of plasma cells and memory B cells. Autoantigens from the salivary gland epithelial cells contribute to the formation of immune complexes, perpetuating the autoimmune response.

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