Nintedanib's unexpected effect on CCR2+ cells

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The image demonstrates a significant decrease in CCR2+ cell accumulation in the lungs of bleomycin-induced fibrosis mice model treated with either propagermanium or nintedanib, as compared to untreated controls.  This visual representation supports the conclusion that both CCR2 inhibition (propagermanium) and nintedanib treatment can limit the progression of lung fibrosis. Image credit: eBioMedicine (2024) DOI: 10.1016/j.ebiom.2024.105431


Pulmonary fibrosis is a serious lung disease where the lung tissue becomes scarred and thick, making it hard to breathe. It’s like the lungs are turning into leather. This can happen for different reasons, and sometimes doctors don’t know why. One thing they do know is that certain cells called immune cells play a big part in causing the damage.

The Role of CCR2+ Cells

Among these immune cells, a type called CCR2+ monocytes are particularly troublesome. These cells come from the bone marrow and travel to the lungs when there's an injury. Once in the lung, they turn into macrophages and release substances that encourage the scarring. It's like they’re sending out signals for the lung to build too much scar tissue.

Doctors have been trying to find ways to stop these cells from causing damage. One approach has been to target these CCR2+ cells directly, to stop them from entering the lungs, or to make them less harmful.

Nintedanib: An Unexpected Hero

Researchers have been studying a drug called nintedanib, which is already used to treat pulmonary fibrosis. The original idea behind nintedanib was that it slowed down the cells that cause the scarring – the fibroblasts. However, this new research has shown that nintedanib does something else that's quite surprising. It also reduces the number of these harmful CCR2+ cells in the lungs. This was a very unexpected finding because nintedanib was not designed to target these immune cells.

How Does Nintedanib Work on CCR2+ Cells?

Scientists looked more closely to see how nintedanib affects these CCR2+ cells. They found that nintedanib doesn’t directly attack the CCR2+ cells or the signals they use to travel to the lungs. Instead, nintedanib seems to make it harder for these cells to move around. The movement of these cells is dependent on another molecule called CCL2, which attracts them to the damaged lung. It seems that nintedanib inhibits CSF1R, which is needed for the movement of the CCR2+ cells in response to CCL2. So, while nintedanib doesn't directly block the signal, it stops the cells from responding to it effectively.

Monitoring the Disease with Imaging

To track the CCR2+ cells in the lungs, scientists developed a special imaging technique called CCR2-PET. This is similar to an X-ray, but it uses a special substance that sticks to the CCR2+ cells so they light up on the scan. This allows the scientists to see where the cells are and how many there are.

Using this new imaging method, they found that:

  • The number of CCR2+ cells was increased in the lungs of mice with lung fibrosis.
  • Both a CCR2 inhibitor and nintedanib reduced the number of CCR2+ cells in the lungs.
  • Nintedanib decreased the signals that attract these cells to the lung, further supporting the mechanism.
  • The CCR2-PET scan could predict how the fibrosis would develop over time.
  • The imaging could also show if a drug was working to reduce the number of harmful cells.

What This Means for Patients

This research has several important implications:

  • It provides a new understanding of how nintedanib works and suggests that its effect on CCR2+ cells is a key mechanism.
  • It highlights the importance of CCR2+ cells in causing lung fibrosis.
  • It introduces a new imaging method, CCR2-PET, that could be used to monitor patients and see if treatment is effective.
  • It suggests that targeting CCR2+ cells, either directly or indirectly, is a viable way to treat fibrosis.

Future Directions

This research opens up exciting new possibilities for treating pulmonary fibrosis. The fact that nintedanib has this previously unknown effect on CCR2+ cells means it may be even more beneficial than doctors previously thought. The CCR2-PET imaging method could become a valuable tool for guiding treatment decisions. It may help doctors to select the right treatment for each patient, and see how well that treatment is working. Further research will be needed to explore all these opportunities and bring new, more effective therapies to people with pulmonary fibrosis.

Additional information: Molecular imaging in experimental pulmonary fibrosis reveals that nintedanib unexpectedly modulates CCR2 immune cell infiltration. eBioMedicine (2024) DOI: 10.1016/j.ebiom.2024.105431

Location: Oxford, UK

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