Immune system's cellular lineage diversity is expanding and quite rapidly. Now we have several types of T cells, several types of NK cells, whole new family of innate lymphoid cells (ILCs), cytokine-secreting B cells, specialized subset of neutrophils using sticky DNA nets to trap the microbes.
Here comes a paper in Science showing a new subset of orphan nuclear receptor Nur77-positive monocytes specializing in protection of lung vasculature from tumor metastases.
First, using reporter mice that tracks Nur77+monocytes (encoded by Nr4a1, a Nr4a1-GFP green mice), the authors showed that after intravenous injection of red fluorescent Lewis Lung Carcinoma cells (LLC-RFP), Nur77+monocytes are rapidly accumulating in the lung vasculature, then slowing down their speed in close proximity to tumor cells.
To confirm that Nur77+monocytes play a role in tumor defense, the authors first repeated the same experiment with total Nr4a1-KO mice, which according to the authors, selectively lack Nur77+monocytes. Nra1-KO mice appeared to harbor more lung metastasis (but not in liver), even if tumor cells [B16 melanoma] were injected subQ.
Similarly, increased tumor metastases (but not primary tumors) were seen with mouse model of spontaneous mammary tumor, MMTV-PyMT, receiving Nr4a1-KO bone marrow transfer, supporting the role of Nur77+ hematopoietic cells in prevention of tumor metastases.
To more specifically address the role of Nur77+monocytes in tumor protection, the authors have used two different myeloid-specific Nr4a1 conditional knockout models, CSF1R-Cre+ Nr4a1fl/fl and LysM-Cre+ Nr4a1fl/fl. In both models, there was an increase in tumor metastases to the lung. Interestingly, T cell-specific Nur77 deletion showed no effect on tumor metastases.
Finally, the authors found that receptor CX3CR1 could play an important role in tumor recognition by Nur77+monocytes.
In summary, this study suggest that there is a specialized monocytes lineage defined by Nr4a1 expression that specifically patrol and protects the lung vasculature against tumor metastases.
David Usharauli
First, using reporter mice that tracks Nur77+monocytes (encoded by Nr4a1, a Nr4a1-GFP green mice), the authors showed that after intravenous injection of red fluorescent Lewis Lung Carcinoma cells (LLC-RFP), Nur77+monocytes are rapidly accumulating in the lung vasculature, then slowing down their speed in close proximity to tumor cells.
To confirm that Nur77+monocytes play a role in tumor defense, the authors first repeated the same experiment with total Nr4a1-KO mice, which according to the authors, selectively lack Nur77+monocytes. Nra1-KO mice appeared to harbor more lung metastasis (but not in liver), even if tumor cells [B16 melanoma] were injected subQ.
Similarly, increased tumor metastases (but not primary tumors) were seen with mouse model of spontaneous mammary tumor, MMTV-PyMT, receiving Nr4a1-KO bone marrow transfer, supporting the role of Nur77+ hematopoietic cells in prevention of tumor metastases.
Finally, the authors found that receptor CX3CR1 could play an important role in tumor recognition by Nur77+monocytes.
In summary, this study suggest that there is a specialized monocytes lineage defined by Nr4a1 expression that specifically patrol and protects the lung vasculature against tumor metastases.
David Usharauli
