PT  - JOURNAL ARTICLE
AU  - Rakesh Kulkarni
AU  - Siti Khadijah Kasani
AU  - Ching-Yen Tsai
AU  - Shu-Yun Tung
AU  - Kun-Hai Yeh
AU  - Chen-Hsin Albert Yu
AU  - Wen Chang
TI  - FAM21 is critical for TLR2/CLEC4E-mediated dendritic cell function against <em>Candida albicans</em>
AID  - 10.26508/lsa.202201414
DP  - 2023 Apr 01
TA  - Life Science Alliance
PG  - e202201414
VI  - 6
IP  - 4
4099  - https://www.life-science-alliance.org/content/6/4/e202201414.short
4100  - https://www.life-science-alliance.org/content/6/4/e202201414.full
SO  - Life Sci. Alliance2023 Apr 01; 6
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.