FAM13A regulates KLRG1 expression and interferon gamma production of natural killer cells

Ni Zeng, Maud Theresine, Christophe Capelle, Neha D. Patil, Cécile Masquelier, Caroline Davril, Alexandre Baron, Djalil Coowar, Xavier Dervillez, Aurélie Poli, Cathy Leonard, Rudi Balling, Markus Ollert, Jacques Zimmer*, Feng Q. Hefeng

*Corresponding author for this work

Research output: Working paperPreprint


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-γ 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.Competing Interest StatementThe authors have declared no competing interest.APCAntigen-presenting cellsARActivating receptorAWSAnimal welfare structureCFSECarboxy fluorescein succinimidyl esterCMCentral memoryCOPDChronic obstructive lung diseaseEMEffector memoryeQTLExpression quantitative trait lociFACSFlow cytometryFam13aFamily with sequence similarity 13, member AFBSFetal bovine serumGWASGenome-wide association studyHETHeterozygousIFN-γInterferon gammaIL-2/-12/-15/-18Interleukin 2/12/15/18IRInhibitory receptorKIRKiller immunoglobulin-like receptorsKLRG1Killer cell lectin-like receptor G1KOKnockoutMFIMean fluorescent intensityMHCMajor histocompatibility complexNKNature KillerPBSPhosphate-buffered salinePCRPolymerase chain reactionpLNperipheral lymph nodesTconvConventional CD4 T cellsTregCD4 regulatory T cellsWTWildtype
Original languageEnglish
Number of pages22
Publication statusPublished - 18 May 2021

Publication series

PublisherCold Spring Harbor Laboratory Press


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