FAM13A regulates maturation and effector functions of natural killer cells

Zeng, N.; Theresine, M.; Capelle, C.; Patil, N.; Masquelier, C.; Davril, C.; Baron, A.; Coowar, D.; Dervillez, X.; Poli, A.; Leonard, C.; Balling, R.; Ollert, M.; Zimmer, J.; He, F. Q.

doi:10.1101/2020.08.26.268490

bioRxiv · 10.1101/2020.08.26.268490

FAM13A regulates maturation and effector functions of natural killer cells

Zeng, N.·Theresine, M.·Capelle, C.·Patil, N.·Masquelier, C.·Davril, C.·Baron, A.·Coowar, D.·Dervillez, X.·Poli, A.·Leonard, C.·Balling, R.·Ollert, M.·Zimmer, J.·He, F. Q.

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Abstract

The polymorphism of the gene FAM13A (family with sequence similarity 13, member A) is strongly linked to the risk of lung cancer and chronic obstructive pulmonary disease, which are among the leading causes of mortality and morbidity in lung-related diseases worldwide. However, the underlying molecular and cellular mechanisms through which FAM13A contributes to the pathogenesis of these diseases largely remain unclear. Here, using a Fam13a knock out (KO) mouse model, we showed that Fam13a depletion upregulated the expression of the terminal differentiation and inhibitory marker, KLRG1 (killer cell lectin-like receptor G1) in natural killer (NK) cells. NK cells from Fam13a-deficient mice showed impaired IFN-{gamma} production either against target tumor cells or following various cytokine cocktail stimulations. Furthermore, the number of lung metastases induced by B16F10 melanoma cells was increased in Fam13a-KO mice. Collectively, our data suggest a key role of FAM13A in regulating NK cell functions, indicating that the key lung-disease risk gene FAM13A might contribute to the pathogenesis of several lung diseases via regulating NK cells.

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Zeng, N., Theresine, M., Capelle, C., Patil, N., Masquelier, C., Davril, C., Baron, A., Coowar, D., Dervillez, X., Poli, A., Leonard, C., Balling, R., Ollert, M., Zimmer, J., He, F. Q.. 2020-08-27. FAM13A regulates maturation and effector functions of natural killer cells. https://doi.org/10.1101/2020.08.26.268490

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