Folr2-KO Mouse

Folr2, also known as Folate Receptor 2, is a protein-coding gene. Folate receptors are important in folate transport, and Folr2 may be involved in processes related to one-carbon metabolism. Folr2-expressing cells, especially macrophages, play crucial roles in immune-related biological processes [5].

In cancer research, a discrete population of FOLR2+ tissue-resident macrophages has been identified in healthy mammary gland and breast cancer primary tumors. These macrophages localize in perivascular areas of the tumor stroma, interact with CD8+ T cells, and efficiently prime effector CD8+ T cells ex vivo. The density of FOLR2+ macrophages in breast tumors positively correlates with better patient survival [1]. In hepatocellular carcinoma, fetal-like (FOLR2) tumor-associated macrophages emerge as a result of onco-fetal reprogramming of the tumor microenvironment [2]. In chronic kidney disease, inflammatory fibroblasts promote the switch of macrophages into FOLR2+ macrophages, and this interaction is involved in kidney fibrosis [3]. In colon cancer, a subset of FOLR2+ macrophages is embedded in plasma cell niches [4]. In gastric cancer, FOLR2+ macrophages possess antitumor immune potential, and their proportion gradually decreases from complete intestinal metaplasia to incomplete intestinal metaplasia and early gastric cancer stages [6]. In lung adenocarcinoma, FOLR2-expressing tumor-associated macrophages may contribute to the formation of an immunosuppressive microenvironment through a specific cell-to-cell trajectory [7]. A population of TIM4+FOLR2+ macrophages localized in tertiary lymphoid structures correlates to an active immune infiltrate across several cancer types, with different phenotypes and prognostic associations [8].

In conclusion, Folr2, especially through its expression in macrophages, is involved in multiple disease-related immune processes, including cancer and chronic kidney disease. The study of Folr2-related macrophage populations in these disease conditions helps to understand the underlying immune-mediated mechanisms, potentially providing new targets for therapeutic interventions.