How many cells were pre-incubated with anti-mouse CD16/CD?

One million cells per sample were pre-incubated with purified anti-mouse CD16/CD32 antibody (Fc BlockTM, 553141, BD Biosciences).

What is the role of NK cells in the control of tumor metastases?

Since NK cells are critical in the control of tumor metastasis [26], the authors induced lung metastasis by intravenous injection of B16F10 melanoma cells into Fam13a whole-body KO and WT littermates.

What is the effect of loss of Fam13a on NK cells?

loss of Fam13a caused a modest but significant decrease in the degranulation capacity per individual NK cell against YAC-1, as indicated by the decreased MFI of CD107a in Fam13a deficient NK cells (Fig 2n).

What did the authors do to get a more comprehensive picture of NK cells?

To get a more comprehensive picture, the authors further analyzed different inhibitory receptors (IR) and activation receptors (AR) of NK cells, whose engagement is critical to regulate and balance NK cell activities.

What is the effect of the decreased number of NK cells in Fam13a KO?

This indicates that both the decreased number and the high level of KLRG1 of NK cells in Fam13a KO mice together aggravate tumor metastasis.

What is the role of NK cells in the control of lung metastases?

Although NK cells are indispensable in suppressing B16F10-induced lung metastasis, the authors hitherto cannot exclude the potential role of other immune cells [30].

Open AccessPosted Content10.1101/2020.08.26.268490

FAM13A regulates maturation and effector functions of natural killer cells

Ni Zeng, +14 more

- 27 Aug 2020

- bioRxiv

TL;DR: FAM13A (family with sequence similarity 13, member A), strongly linked to the risk of prominent death-causing lung diseases, critically modulated NK cell maturation and effector functions and immune protection against tumor metastasis is shown.

Abstract: 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.

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1. What are the contributions mentioned in the paper "Fam13a regulates klrg1 expression and interferon gamma production of natural killer cells" ?

Here, using a Fam13a knock out ( KO ) mouse model, the authors 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.. Furthermore, the number of lung metastases induced by B16F10 melanoma cells was increased in Fam13a-KO mice.. Collectively, their 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.

2. What is the effect of Fam13a on NK cells?

after an in vivo pre-activation of NK cells via the TLR3 agonist poly(I:C), Fam13a-KO NK cells produced less IFN-γ compared to WT NK cells.

3. What is the effect of Fam13a on COPD?

Functional studies have revealed that Fam13a depletion reduces the susceptibility to COPD via inhibiting the WNT/β-catenin pathway in a mouse model [13].

4. What type of mice were used in the experiments?

The Fam13a-/- (KO), Fam13a+/- (HET) and Fam13a+/+ (WT) mice used in the experiments were age- and gender-matched littermates generated from Fam13a+/- heterozygous breeding pairs.

Fig 3. Fam13a deficiency aggravates lung metastasis induced by melanoma cells. (a) Schematic of the experimental setup for lung metastasis model induced by B16F10 melanoma cells. (b) Representative photographs of freshly isolated lungs after B16F10 cell inoculation. (c) Quantified metastatic foci of freshly isolated lungs after B16F10 cell inoculation (pooled KO, n=21; pooled WT, n=23). (d) Representative FACS plot of NKp46 and NK1.1 expression on Fam13a KO and WT CD3-CD19- living singlet lymphocytes. (e, g) Percentage of NKp46+NK1.1+ NK cells out of CD3-CD19- cells in spleen (e) or lung (g) of Fam13a KO and WT littermates. (f) Absolute number of NKp46+NK1.1+ NK cells out of CD3-CD19- cells in spleen of Fam13a KO and WT littermates. (h) Representative FACS plot of KLRG1 and NK1.1 expression on Fam13a KO and WT NK cells in the spleen. (i, j) Percentage of KLRG1+ NK cells among total NK cells in spleen (i) or lung (j) (KO, n=3, WT, n=4). Data are mean ± s.d. The p-values were calculated by a two-tailed Student’s t-test. n.s. or unlabeled, not significant, *p<=0.05, **p <=0.01 and ***p <=0.001.

Fig 2. Fam13a deficiency impairs NK-cell IFN-γ production following in vitro or ex vivo stimulation. (a) Schematic of the experimental setup to stimulate NK cells with different cytokine cocktails. (b) Percentage of living cells after 5-day expansion in the presence of IL-2 (KO, n=10; WT, n=7). (c) Percentage of NK1.1+ NK cells after 5-day expansion in the presence of IL-2 (KO, n=10; WT, n=8). (d) Representative FACS histogram overlay of IFN-γ production of Fam13a KO (red line) and WT (black line) NK cells following 5-day IL-2 expansion and IL-2, IL-12 and IL-15 re-stimulation. (e) Percentage of IFN-γ producing cells among total NK cells after IL-2, IL-12 and IL-15 re-stimulation (KO, n=12; WT, n=9). (f) Representative FACS histogram overlay of IFN-γ production of Fam13a KO (red line) and WT (black line) NK cells after 5-day IL-2 expansion and IL-2, IL-12 and IL-18 re-stimulation. (g) Percentage of IFN-γ producing cells among total NK cells after IL2, IL-12 and IL-18 re-stimulation. (h) Schematic of the experimental setup to analyze the ex-vivo degranulation capacity of NK cells. Fam13a KO or WT littermates were injected intraperitoneally (i.p.) with 150 µg poly(I:C) or PBS and then the next day splenocytes were incubated with YAC-1 cells to evaluate NK cell IFN-γ production and degranulation. (i) Percentage of IFN-γ producing NK cells of Fam13a KO and WT NK cells against YAC-1 tumor cells. (j) Absolute number of IFN-γ producing NK cells of Fam13a KO and WT NK cells against YAC-1 tumor cells. (k) Geometric mean of IFN-γ expression intensity in total IFN-γ+ NK cells of Fam13a KO and WT NK cells. (l) Percentage of CD107a producing NK cells of Fam13a KO and WT NK cells against YAC-1 tumor cells. (m) Absolute number of CD107a producing NK cells of Fam13a KO and WT NK

Citations

•Journal Article

Association of FAM13A polymorphisms with COPD and COPD-related phenotypes in Han Chinese

Bo Wang, +7 more

- 01 Sep 2013

- European Respiratory Journal

TL;DR: Wang et al. as mentioned in this paper investigated whether FAM13A polymorphisms would be associated with COPD susceptibility and COPD-related phenotypes in Han Chinese, and they found that the FAM13a locus might be a contributor to chronic obstructive pulmonary disease susceptibility.

...read moreread less

References

Journal Article•10.1146/ANNUREV-IMMUNOL-031210-101324

Natural Innate and Adaptive Immunity to Cancer

Matthew D. Vesely, +6 more

- 22 Mar 2011

- Annual Review of Immunology

TL;DR: Current experimental and human clinical data supporting a cancer immunoediting process that provide the fundamental basis for further study of immunity to cancer and for the rational design of immunotherapies against cancer are discussed.

...read moreread less

2.1K

•Journal Article•10.1182/BLOOD-2007-09-077438

Human natural killer cells

Michael A. Caligiuri

- 01 Aug 2008

- Blood

TL;DR: There has been a substantial gain in understanding of what and how NK-cells "see," lending important insights into their functions and purpose in normal immune surveillance.

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1.8K

Journal Article•10.1016/J.JIM.2004.08.008

CD107a as a functional marker for the identification of natural killer cell activity

Galit Alter, +2 more

- 01 Nov 2004

- Journal of Immunological Methods

TL;DR: It is suggested that employing CD107a as a marker of NK cell functional activity may allow for the identification of a large fraction of activated NK cells that may degranulate in the absence of cytokine secretion.

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Journal Article•10.1038/NATURE03847

Licensing of natural killer cells by host major histocompatibility complex class I molecules

Sung Jin Kim, +10 more

- 04 Aug 2005

- Nature

TL;DR: It is demonstrated that NK cells acquire functional competence through ‘licensing’ by self-MHC molecules, which results in two types of self-tolerant NK cells—licensed or unlicensed—and may provide new insights for exploiting NK cells in immunotherapy.

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•Journal Article•10.1016/J.CELL.2018.10.022

Impact of Genetic Polymorphisms on Human Immune Cell Gene Expression.

Benjamin J Schmiedel, +16 more

- 29 Nov 2018

- Cell

TL;DR: The DICE project identified cis-eQTLs for a total of 12,254 unique genes, which represent 61% of all protein-coding genes expressed in these cell types and found that biological sex is associated with major differences in immune cell gene expression in a highly cell-specific manner.

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FAM13A regulates maturation and effector functions of natural killer cells

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AI Agents for this Paper

Most frequently asked questions

1. What are the contributions mentioned in the paper "Fam13a regulates klrg1 expression and interferon gamma production of natural killer cells" ?

2. What is the effect of Fam13a on NK cells?

3. What is the effect of Fam13a on COPD?

4. What type of mice were used in the experiments?

5. How many cells were pre-incubated with anti-mouse CD16/CD?

6. What is the role of NK cells in the control of tumor metastases?

7. What is the effect of loss of Fam13a on NK cells?

8. What did the authors do to get a more comprehensive picture of NK cells?

9. What is the effect of the decreased number of NK cells in Fam13a KO?

10. What is the role of NK cells in the control of lung metastases?

Figures

Citations

Association of FAM13A polymorphisms with COPD and COPD-related phenotypes in Han Chinese

References

Natural Innate and Adaptive Immunity to Cancer

Human natural killer cells

CD107a as a functional marker for the identification of natural killer cell activity

Licensing of natural killer cells by host major histocompatibility complex class I molecules

Impact of Genetic Polymorphisms on Human Immune Cell Gene Expression.

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