Enhanced MHC Class‐II Expression in Fibroblastic Reticular Cells Associates with Maturation

Autoimmunity can be initiated by autoreactive T cells that escaped central and peripheral tolerance induction. Peripheral tolerance in lymph nodes (LNs) is maintained by fibroblastic reticular cells (FRCs) via self‐antigen presentation in major histocompatibility complex (MHC) class II. FRCs can be divided into various subsets, with specific markers, functions, and locations. FRCs located in the T‐cell zone (TRCs) can express genes for antigen presentation in MHC class‐II, for example, H2‐Ab1 and Cd74, as well as the immune inhibitory ligand Cd200. However, whether this can be linked to MHC class‐II protein expression and thus tolerance is unknown. By combining scRNAseq on murine FRCs with protein staining for extracellular MHC class‐II, we confirm that murine TRCs have the highest MHC class‐II transcript levels, while protein levels are elevated in multiple FRC subsets. Gene expression for MHC class‐II, as well as Bst1 and Cd200, gradually increases along the pseudotime trajectory, with TRCs representing the end, indicating maturation. Finally, we validated in fresh LN cell suspensions that MHC class‐II protein expression is associated with murine BST1+ FRCs, independent of CD200, and with human BST1+CD200+ TRCs. This mature FRC subset, equipped to maintain peripheral tolerance, could be an interesting target for therapies against autoimmune diseases.

• Publication year

  2025

• Venue

  European Journal of Immunology

• Publication date

  2025-11-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1002/eji.70086PMID 41211809PMCID 12599485
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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