Cd74, also known as the MHC class II invariant chain (Ii), is a non-polymorphic type II transmembrane glycoprotein. It serves as a chaperone for MHC class II molecules in antigen presentation. Additionally, it is a high-affinity receptor for macrophage migration inhibitory factor (MIF), D-dopachrome tautomerase (D-DT/MIF-2) and bacterial proteins. The activation of the CD74/CD44 receptor complex can trigger multiple intracellular signal pathways such as ERK1/2, PI3K-Akt, NFκB, and AMPK, playing important roles in immune-related processes and diseases [1].

Cd74 genetic deletion in human primary Tregs reveals that CD74KO Tregs have defects in actin cytoskeleton and intracellular organelle organization. Intratumoral CD74KO Tregs show decreased activation, reduced Foxp3 expression, and low tumor accumulation, leading to accelerated tumor rejection in female mice, indicating CD74 is a specific regulator of tumor-infiltrating Tregs [2]. Interference with MIF/CD74 signaling or CD74 deficiency protected from crescentic glomerulonephritis, while CD74 may protect from interstitial kidney fibrosis [3].

In conclusion, Cd74 is crucial in antigen presentation, immune cell regulation, and various disease-related processes. Gene-knockout models, such as CD74KO in Tregs and in the context of kidney diseases, have been instrumental in revealing its role in tumor-immune regulation and kidney disease progression, providing insights into potential therapeutic targets for related diseases.