Graduate Student Univ. of Oklahoma Hlth. Sci. Ctr. Oklahoma City, Oklahoma, United States
Disclosure(s):
Aneta Pankow, MS: No financial relationships to disclose
Introduction/Rationale: Group 2 innate lymphoid cells (ILC2s) are innate counterparts of T cells, and share with T cells transcription factors and effector cytokines. Unlike T cells, they lack antigen-specific receptors, allowing them to respond rapidly to tissue changes during infection, damage, or allergen exposure. Residing in mucosal surfaces, ILC2s also regulate tissue homeostasis. While ILC2s are thought to originate from the bone marrow, our lab has shown that the thymus contributes to ILC2 pools in various tissues.
Methods: Our previous data suggested that ILC2s of thymic origin express Cd3 genes, therefore we generated Cd3giCre mice and crossed them with Rosa26stop-ZsGreen, to label Cd3g-expressing ILC2s with ZsGreen (ZsG). ZsG signal can be detected by flow cytometry, and RNA sequencing revealed differences between ZsG+ and ZsG- ILC2s.
Results: We found ZsG expression begins in the thymus at the early stage of T cell development and persists in mature T cells. The absence of ZsG signal in bone marrow progenitors, myeloid and B cell lineages indicates the thymus specificity of Cd3giCre. ZsG+ ILC2s are enriched in neonatal lungs, when lung alveolarization occurs, which suggests a supporting role of ILC2s in lung development and remodeling. RNA sequencing revealed that ZsG+ ILC2s express high levels of Il13, Il4, and Klrg1, indicating their higher activation status. ZsG+ ILC2s also harbor rearranged Tcrb, Tcrg and Tcrd genes, suggesting shared developmental pathways with T cells in the thymus. We used naphthalene lung injury model to explore the role of ILC2s in the lung repair in neonatal mice, which showed that ILC2s are essential for macrophage polarization, highlighting their role in tissue repair.
Conclusion: This study reveals a previously unrecognized thymic contribution to ILC2s early in life, when bone marrow is not yet fully functional. These findings may help explain differences in pediatric versus adult immunity, and provide hints to therapeutic strategies.
