Neonatal lung group 2 innate lymphoid cells and their role in mediating type 2 immunity and allergen sensitization

Catherine Steer
Airway allergic diseases predominantly originate from early life exposure to allergens, but the mechanism behind this is unclear. Group 2 innate lymphoid cells (ILC2s) are critical for innate and adaptive immune responses to airway allergens in adult mice. Therefore, I hypothesized that ILC2s play an essential role in neonatal lung immunity. ILC2s quickly seed the mouse lung after birth and begin proliferating and producing IL-13 and IL-5 around postnatal day 10-14, inducing eosinophilia.
more » ... eosinophilia. Neonatal pups deficient for IL-33, an epithelial-derived alarmin that activates ILC2s, have fewer lung ILC2s and eosinophils at day 10 than wildtype (WT) pups. The amount of IL-33 in WT pups is high at day 10 and decreases after day 15, correlating with a contraction of ILC2s into adulthood. Thus, spontaneous release of IL-33 into neonatal lungs provokes activation of ILC2s and eosinophilia. Neonatal ILC2s are more responsive to intranasal (I.N) protease allergen papain than adult ILC2s and respond more intensely upon a secondary challenge in adulthood. Furthermore, ILC2s drive neonatal Th2-biased cell differentiation. I.N OVA antigen treatments into day 10 ILC2-deficient pups transplanted with OT-II adult CD4⁺ T cells results in fewer IL-4⁺IL-13⁺ CD4⁺ OT-II T cells in the lung-draining lymph node than in WT pups. Therefore, ILC2s play a role in neonatal sensitization to allergens leading to persistent allergic disease. The majority of neonatal ILC2s incorporate BrdU, and the BrdU-labeled neonatal ILC2s persist into adulthood, comprising almost 30% of adult lung ILC2s. To determine the effect of neonatal IL-33 exposure on ILC2 function, I.N IL-33 was given to IL-33-deficient (KO) and wildtype (WT) adult mice. While there was no difference in the number of lung ILC2s, there were fewer IL-5⁺IL-13⁺ ILC2s in IL-33KO than IL-33WT mice. I.N IL-33 into IL-33KO pups rescued the impaired response in adulthood. Microarray analysis showed cell-intrinsic differences between IL-33KO and IL-33WT ILC2s. Overall, weak activation by endo [...]
doi:10.14288/1.0379253 fatcat:zrrnthnnoncztei4njqua577jq