Preprint identifies cryptochrome clock genes as regulators of alveolar integrity and lung immune homeostasis

A preprint posted to bioRxiv describes findings from researchers who studied mice lacking both Cryptochrome 1 and Cryptochrome 2 (Cry1/2), the core negative-feedback components of the mammalian circadian clock. Animals with this double knockout (dKO) spontaneously developed pathology resembling chronic obstructive pulmonary disease (COPD), including airspace enlargement consistent with emphysema, increased lung compliance, and evidence of chronic pulmonary inflammation.

The authors report that Cry1 and Cry2 appear to be essential for maintaining normal alveolar epithelial cell proliferation and for sustaining pulmonary immune homeostasis. In their absence, the balance between tissue repair and inflammatory damage shifts in a manner that the authors propose may mechanistically connect circadian disruption — a feature of shift work, sleep disorders, and ageing — to the accelerated lung tissue destruction seen in COPD.

While circadian disruption has previously been epidemiologically associated with elevated COPD risk, the cellular mechanisms had remained poorly characterised. The authors suggest their Cry1/2 dKO model provides a tractable system for dissecting these pathways.

This work is a preprint and has not yet undergone peer review. Findings should be interpreted accordingly. The research adds to a growing body of work linking core clock genes to tissue-maintenance functions beyond timekeeping.