| First Author | Guedes JR | Year | 2023 |
| Journal | Neuron | Volume | 111 |
| Issue | 21 | Pages | 3435-3449.e8 |
| PubMed ID | 37918358 | Mgi Jnum | J:342621 |
| Mgi Id | MGI:7550289 | Doi | 10.1016/j.neuron.2023.09.031 |
| Citation | Guedes JR, et al. (2023) IL-4 shapes microglia-dependent pruning of the cerebellum during postnatal development. Neuron 111(21):3435-3449.e8 |
| abstractText | Interleukin-4 (IL-4) is a type 2 cytokine with pleiotropic functions in adaptive immunity, allergies, and cognitive processes. Here, we show that low levels of IL-4 in the early postnatal stage delineate a critical period in which microglia extensively prune cerebellar neurons. Elevating the levels of this cytokine via peripheral injection, or using a mouse model of allergic asthma, leads to defective pruning, permanent increase in cerebellar granule cells, and circuit alterations. These animals also show a hyperkinetic and impulsive-like phenotype, reminiscent of attention-deficit hyperactivity disorder (ADHD). These alterations are blocked in Il4ralpha(fl/fl)::Cx3cr1-CreER mice, which are deficient in IL-4 receptor signaling in microglia. These findings demonstrate a previously unknown role for IL-4 during a neuroimmune critical period of cerebellar maturation and provide a first putative mechanism for the comorbidity between allergic disease and ADHD observed in humans. |
