ROLE OF THE IMMUNE SYSTEM AND NEUROIMMUNE INTERACTIONS IN THE ONSET OF NEURODEVELOPMENTAL DISORDERS ASSOCIATED WITH PREMATURITY

Premature birth (<37 weeks of gestation) remains a leading cause of mortality and disability in children under five. Maternal infection and systemic inflammation are major risk factors for both prematurity and neonatal brain injury, often leading to neurodevelopmental disorders (NDDs). Using a mouse model of encephalopathy of prematurity induced by perinatal inflammation through systemic IL-1β injections (P1–P5), we characterized peripheral innate and adaptive immune responses from birth to P45.
Systemic inflammation caused early depletion of circulating polynuclear cells and monocytes at P1, consistent with their infiltration into the brain. Monocytes displayed sustained activation, as evidenced by MHCII expression throughout the study period. Regarding adaptive immunity, IL-1β–treated mice showed early peripheral B and T lymphocyte expansion at P1, followed by a decline after inflammation cessation, and persistent activation of CD4⁺ T cells one week later. Between P5 and P8, systemic inflammation disrupted the TH1/TH2 balance, altering adaptive immune polarization.
In the neonatal brain, residual T cells were detected under physiological conditions from P1 onward, but inflammatory stimulation perturbed this steady state. Chemokine profiling revealed strong upregulation of CCL2, CCL3, CCL4, CCL5, and CCL11 in IL-1β–treated pups, potentially driving altered recruitment and composition of NK and T cell subsets.
Overall, our findings reveal that perinatal inflammation profoundly disturbs immune homeostasis from early postnatal stages to adolescence. Ongoing spatial analyses of immune cell populations in the brain aim to clarify their interactions with glial cells and inform future neuroprotective strategies.