Human inherited CCR2 deficiency underlies progressive polycystic lung disease. (https://pubmed.ncbi.nlm.nih.gov/38157855/)
These scientists have discovered a lung disease in some children that is caused by a problem with a specific gene called CCR2. This gene helps a type of immune cell called monocytes move to the lungs and other parts of the body when there is an infection.
In this study, the scientists found that nine children from different families had a lung disease called pulmonary alveolar proteinosis (PAP). They also had polycystic lung disease, which means they had many small cysts in their lungs. These children also had frequent infections, including a specific type called bacillus Calmette Guerin (BCG) disease.
The scientists looked closely at the CCR2 gene in these children and found that it was not working properly. Some children had two copies of a gene variant that was not working, while others had one copy of this variant and one copy of a different variant.
Because of these gene variants, the monocytes in these children's bodies couldn't respond properly to a chemical signal called CCL-2 that helps them move. This meant that the monocytes couldn't go to the lungs and other infected areas to fight off infections.
The scientists also found that these children had high levels of CCL-2 in their blood, which could be used as a test to identify other children with similar lung or mycobacterial diseases.
Interestingly, other parts of the children's immune system were not affected by this gene problem. Their blood cells and immune responses to certain signals were normal. However, the number of a specific type of immune cell called alveolar macrophages was reduced by about half.
In conclusion, these scientists discovered that a specific gene problem called CCR2 deficiency can cause lung diseases like PAP and polycystic lung disease, as well as recurrent infections. This gene problem affects the ability of monocytes to move to the lungs and infected tissues, and it can be diagnosed by measuring the levels of a chemical called CCL-2 in the blood.
Neehus AL., Carey B., Landekic M., Panikulam P., Deutsch G., Ogishi M., Arango-Franco CA., Philippot Q., Modaresi M., Mohammadzadeh I., Corcini Berndt M., Rinchai D., Le Voyer T., Rosain J., Momenilandi M., Martin-Fernandez M., Khan T., Bohlen J., Han JE., Deslys A., Bernard M., Gajardo-Carrasco T., Soudee C., Le Floc'h C., Migaud M., Seeleuthner Y., Jang MS., Nikolouli E., Seyedpour S., Begueret H., Emile JF., Le Guen P., Tavazzi G., Colombo CNJ., Marzani FC., Angelini M., Trespidi F., Ghirardello S., Alipour N., Molitor A., Carapito R., Mazloomrezaei M., Rokni-Zadeh H., Changi-Ashtiani M., Brouzes C., Vargas P., Borghesi A., Lachmann N., Bahram S., Crestani B., Pahari S., Schlesinger LS., Marr N., Bugonovic D., Boisson-Dupuis S., Beziat V., Abel L., Borie R., Young LR., Deterding R., Shahrooei M., Rezaei N., Parvaneh N., Craven D., Gros P., Malo D., Sepulveda FE., Nogee LM., Aladjidi N., Trapnell BC., Casanova JL., Bustamante J. Human inherited CCR2 deficiency underlies progressive polycystic lung disease. Cell. 2024 Jan 18;187(2):390-408.e23. doi: 10.1016/j.cell.2023.11.036. Epub 2023 Dec 28.