Browsing by Author "Stier, Matthew T."

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    IL-33 promotes the egress of group 2 innate lymphoid cells from the bone marrow
    (Rockefeller University Press, 2018-01-02) Stier, Matthew T.; Zhang, Jian; Goleniewska, Kasia; Cephus, Jacqueline Y.; Rusznak, Mark; Wu, Lan; Kaer, Luc Van; Zhou, Baohua; Newcomb, Dawn C.; Peebles, R. Stokes, Jr.; Pediatrics, School of Medicine
    Group 2 innate lymphoid cells (ILC2s) are effector cells within the mucosa and key participants in type 2 immune responses in the context of allergic inflammation and infection. ILC2s develop in the bone marrow from common lymphoid progenitor cells, but little is known about how ILC2s egress from the bone marrow for hematogenous trafficking. In this study, we identified a critical role for IL-33, a hallmark peripheral ILC2-activating cytokine, in promoting the egress of ILC2 lineage cells from the bone marrow. Mice lacking IL-33 signaling had normal development of ILC2s but retained significantly more ILC2 progenitors in the bone marrow via augmented expression of CXCR4. Intravenous injection of IL-33 or pulmonary fungal allergen challenge mobilized ILC2 progenitors to exit the bone marrow. Finally, IL-33 enhanced ILC2 trafficking to the lungs in a parabiosis mouse model of tissue disruption and repopulation. Collectively, these data demonstrate that IL-33 plays a critical role in promoting ILC2 egress from the bone marrow.
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    Respiratory syncytial virus infection activates IL-13–producing group 2 innate lymphoid cells through thymic stromal lymphopoietin
    (Elsevier, 2016-09) Stier, Matthew T.; Bloodworth, Melissa H.; Toki, Shinji; Newcomb, Dawn C.; Goleniewska, Kasia; Boyd, Kelli L.; Quitalig, Marc; Hotard, Anne L.; Moore, Martin L.; Hartert, Tina V.; Zhou, Baohua; McKenzie, Andrew N.; Peebles Jr., R. Stokes; Department of Pediatrics, IU School of Medicine
    BACKGROUND: Respiratory syncytial virus (RSV) is a major health care burden with a particularly high worldwide morbidity and mortality rate among infants. Data suggest that severe RSV-associated illness is in part caused by immunopathology associated with a robust type 2 response. OBJECTIVE: We sought to determine the capacity of RSV infection to stimulate group 2 innate lymphoid cells (ILC2s) and the associated mechanism in a murine model. METHODS: Wild-type (WT) BALB/c, thymic stromal lymphopoietin receptor (TSLPR) knockout (KO), or WT mice receiving an anti-TSLP neutralizing antibody were infected with the RSV strain 01/2-20. During the first 4 to 6 days of infection, lungs were collected for evaluation of viral load, protein concentration, airway mucus, airway reactivity, or ILC2 numbers. Results were confirmed with 2 additional RSV clinical isolates, 12/11-19 and 12/12-6, with known human pathogenic potential. RESULTS: RSV induced a 3-fold increase in the number of IL-13-producing ILC2s at day 4 after infection, with a concurrent increase in total lung IL-13 levels. Both thymic stromal lymphopoietin (TSLP) and IL-33 levels were increased 12 hours after infection. TSLPR KO mice did not mount an IL-13-producing ILC2 response to RSV infection. Additionally, neutralization of TSLP significantly attenuated the RSV-induced IL-13-producing ILC2 response. TSLPR KO mice displayed reduced lung IL-13 protein levels, decreased airway mucus and reactivity, attenuated weight loss, and similar viral loads as WT mice. Both 12/11-19 and 12/12-6 similarly induced IL-13-producing ILC2s through a TSLP-dependent mechanism. CONCLUSION: These data demonstrate that multiple pathogenic strains of RSV induce IL-13-producing ILC2 proliferation and activation through a TSLP-dependent mechanism in a murine model and suggest the potential therapeutic targeting of TSLP during severe RSV infection.