RT Journal Article SR Electronic T1 FAM21 is critical for TLR2/CLEC4E-mediated dendritic cell function against Candida albicans JF Life Science Alliance JO Life Sci. Alliance FD Life Science Alliance LLC SP e202201414 DO 10.26508/lsa.202201414 VO 6 IS 4 A1 Rakesh Kulkarni A1 Siti Khadijah Kasani A1 Ching-Yen Tsai A1 Shu-Yun Tung A1 Kun-Hai Yeh A1 Chen-Hsin Albert Yu A1 Wen Chang YR 2023 UL https://www.life-science-alliance.org/content/6/4/e202201414.abstract AB FAM21 (family with sequence similarity 21) is a component of the Wiskott–Aldrich syndrome protein and SCAR homologue (WASH) protein complex that mediates actin polymerization at endosomal membranes to facilitate sorting of cargo-containing vesicles out of endosomes. To study the function of FAM21 in vivo, we generated conditional knockout (cKO) mice in the C57BL/6 background in which FAM21 was specifically knocked out of CD11c-positive dendritic cells. BMDCs from those mice displayed enlarged early endosomes, and altered cell migration and morphology relative to WT cells. FAM21-cKO cells were less competent in phagocytosis and protein antigen presentation in vitro, though peptide antigen presentation was not affected. More importantly, we identified the TLR2/CLEC4E signaling pathway as being down-regulated in FAM21-cKO BMDCs when challenged with its specific ligand Candida albicans. Moreover, FAM21-cKO mice were more susceptible to C. albicans infection than WT mice. Reconstitution of WT BMDCs in FAM21-cKO mice rescued them from lethal C. albicans infection. Thus, our study highlights the importance of FAM21 in a host immune response against a significant pathogen.