Gene of the Month – December: CCR2

Identification of biallelic variants in the CCR2 gene and subsequent functional investigations revealed a previously undescribed mechanism leading to a complex and progressive lung disease. An international study recently published in Cell identified disease-causing variants in CCR2 in nine children with pulmonary alveolar proteinosis, a rare lung disease, associated with chronic inflammation and recurrent infections. The homozygous and compound heterozygous CCR2 variations cause a complete loss of the encoded protein’s function.

CCR2, a receptor protein, is mainly expressed on monocytes and binds the chemokine CCL2. This binding activates a signaling cascade important for recruiting monocytes to infected or injured tissue and for maturation of macrophages as essential parts of the innate immune system. The researchers found that the identified CCR2 variants impair migration of monocytes and thus reduce the number of mature macrophages in the lungs. From the results of their investigations they conclude that CCR2 deficiency was responsible for the high concentrations of CCL2 determined in their patients. A high CCL2 blood level might thus provide a diagnostic test for children with unexplained lung disease.

Neehus AL, Carey B, Landekic M … Bustamante J. Human inherited CCR2 deﬁciency underlies progressive polycystic lung disease. Cell. 2023 Dec 20:S0092-8674(23)01323-5. doi: 10.1016/j.cell.2023.11.036. Epub ahead of print.

Article in PubMed

Gene of the Month – December: CCR2

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