CARD11, a lymphoid lineage-specific scaffold protein, is crucial for integrating antigen-receptor engagement with downstream signaling to NF-κB and other outputs in lymphocytes [2,4]. It forms the CARD11-BCL10-MALT1 (CBM) signaling complex, which regulates NF-κB activation and mRNA stability in T-and B-cell receptor-induced gene expression [4]. Genetic models, such as KO/CKO mouse models, are valuable for studying CARD11.

Mouse models with CARD11 deficiencies or those lacking CARD11-associated signaling components generally have Treg defects [1]. CARD11 is essential for the development and function of thymic Tregs, as some mouse models with such deficiencies develop overt autoimmunity and inflammatory disease, while others do not [1]. In addition, a germline N-ethyl-N-nitrosourea (ENU)-induced Card11M365K mutation in mice increased B and T lymphocyte activation and proliferation following antigen receptor stimulation, and caused over-accumulation of activated T cells, TREG, TFH, and TFR cells [3].

In conclusion, CARD11 is vital for lymphocyte function, especially in Treg development and activation. Mouse models with CARD11 mutations have provided insights into its role in autoimmunity, inflammation, and T-cell malignancies, highlighting its significance in understanding immune-related disease mechanisms.