FAM13A regulates maturation and effector functions of natural killer cells

The education or licensing process is essentially required for the proper anti-tumor function of natural killer (NK) cells. Although several models for education have been proposed, the genetic factors regulating these processes still remain largely elusive. Here we show that FAM13A (family with seq...

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Bibliographic Details
Published inbioRxiv
Main Authors Zeng, Ni, Theresine, Maud, Capelle, Christophe, Patil, Neha, Masquelier, Cecile, Davril, Caroline, Baron, Alexandre, Coowar, Djalil, Dervillez, Xavier, Poli, Aurelie, Leonard, Cathy, Balling, Rudi, Ollert, Markus, Zimmer, Jacques, He, Feng Q
Format Paper
LanguageEnglish
Published Cold Spring Harbor Cold Spring Harbor Laboratory Press 27.08.2020
Subjects
Antitumor activity
Cell culture
Cell differentiation
Chronic obstructive pulmonary disease
Degranulation
Genetic factors
Interferon
KLRG1 protein
Lung cancer
Lung diseases
Melanoma
Metastases
Natural killer cells
Obstructive lung disease
γ-Interferon
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Summary:The education or licensing process is essentially required for the proper anti-tumor function of natural killer (NK) cells. Although several models for education have been proposed, the genetic factors regulating these processes still remain largely elusive. Here we show that FAM13A (family with sequence similarity 13, member A), strongly linked to the risk of prominent death-causing lung diseases, i.e., lung cancer and chronic obstructive pulmonary disease, critically modulated NK cell maturation and effector functions. Fam13a depletion promoted NK cell maturation, KLRG1 (killer cell lectin-like receptor G1) expression in NK cells and NK terminal differentiation in homeostatic mice. NK cells from Fam13a-deficient mice had impaired IFN-γ production and degranulation. Strikingly, the number of lung metastases induced by B16F10 melanoma cells was increased in Fam13a-deficient mice. Collectively, our data reveal a pivotal role of FAM13A in slowing down NK maturation, but promoting NK cell effector functions and immune protection against tumor metastasis. Competing Interest Statement The authors have declared no competing interest.
DOI:10.1101/2020.08.26.268490