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. 2022 Dec;19(12):1429-1431.
doi: 10.1038/s41423-022-00908-8. Epub 2022 Aug 19.

Immunopathogenesis of idiopathic nephrotic syndrome

B Savas  1 , F Fofana  1 , S Le Gouvello  1 , A Pawlak  1 , D Sahali  2   3 , M Ollero  1
Affiliations

Immunopathogenesis of idiopathic nephrotic syndrome

B Savas et al. Cell Mol Immunol. 2022 Dec.
No abstract available

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
CMIP inhibits proximal T-cell signaling. A Costimulation by anti-CD3/CD28 antibodies mimics T-cell activation induced by ligation of the TCR to a peptide bound to a major histocompatibility complex (MHC) class II-antigen. In both cases, signal 1 (dependent on TCR ligation) and signal 2 (CD28 costimulation) trigger rapid Src kinase-mediated phosphorylation of the immunoreceptor tyrosine-based activation motif (ITAM), a conserved domain of signal-transducing chains of the TCR complex. Phosphorylated ITAMs serve as binding sites for the ZAP-70 kinase, which is activated by phosphorylation by the Src kinase Lck, resulting in stability of the ITAM-ZAP-70 interaction. The clustering of active TCRs and the recruitment of Lck/Fyn and ZAP-70 occur in lipid rafts (LRs), which are plasma membrane microdomains that are enriched in cholesterol and glycosphingolipids and serve as signaling platforms. Activation of ZAP-70 induces phosphorylation of the transmembrane adapter molecule LAT (linker for activation of T cells) and leukocyte phosphoprotein of 76 kDa (SLP-76) at multiple tyrosine residues, contributing to the assembly of a signaling complex in LRs through protein‒protein or protein–lipid interactions, which in turn leads to cytoskeletal reorganization, the formation of immunological synapses and efficient signal transmission from LRs to downstream signaling cascades, ultimately resulting in the activation of transcription factors such as NF-kB, NFAT, and AP-1. B Overexpression of CMIP inhibits the activation of Src kinases and ZAP-70, suggesting that CMIP interferes with proximal T-cell signaling and prevents the clustering of lipid rafts, reorganization of the cytoskeleton and activation of downstream signaling cascades
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References

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Supplementary concepts