Myeloid-IL4Rα is an indispensable link in IL-33-ILCs-IL-13-IL4Rα axis of eosinophil recruitment in murine lungs

Sonika Patial, Department of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, 1909 Skip Bertman Drive, Baton Rouge, LA, 70803, USA.
Brandon W. Lewis, Department of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, 1909 Skip Bertman Drive, Baton Rouge, LA, 70803, USA.
Thao Vo, Department of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, 1909 Skip Bertman Drive, Baton Rouge, LA, 70803, USA.
Ishita Choudhary, Department of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, 1909 Skip Bertman Drive, Baton Rouge, LA, 70803, USA.
Kshitiz Paudel, Department of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, 1909 Skip Bertman Drive, Baton Rouge, LA, 70803, USA.
Yun Mao, Department of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, 1909 Skip Bertman Drive, Baton Rouge, LA, 70803, USA.
Dhruthi Singamsetty, Department of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, 1909 Skip Bertman Drive, Baton Rouge, LA, 70803, USA.
Frank Brombacher, International Center for Genetic Engineering and Biotechnology, Cape Town Component & University of Cape Town, Health Science Faculty, IDM, Cape Town, South Africa.
Yogesh Saini, Department of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, 1909 Skip Bertman Drive, Baton Rouge, LA, 70803, USA. ysaini@lsu.edu.

Document Type

Article

Publication Date

7-29-2021

Abstract

Increased eosinophil recruitment is a hallmark feature of eosinophilic disorders. Here, we delineated the key molecular and cellular players involved in physiological eosinophilic recruitment during normal postnatal lung development in mice. Physiological eosinophilic recruitment was consistently present in 7-, 10-, and 15-day-old neonatal mice, but not in 42-day-old mice. This feature was completely abolished in interleukin 33 (IL-33)-, interleukin 2 receptor gamma chain (IL2rγ)-, and interleukin 4 receptor alpha (IL4Rα)-knockout mice, but not in recombination activating gene 1 (Rag1)-knockout mice demonstrating an indispensable role for IL-33, innate lymphoid cells (ILCs), and IL4Rα in eosinophil recruitment. Interestingly, myeloid-specific IL4Rα-deficient (mye-IL4Rα) mice had significantly reduced eosinophilia in the airspaces that was associated with reduced levels of IL-4 and IL-5 in the bronchoalveolar lavage fluid (BALF). Further, we tested the effect of myeloid-specific IL4Rα deficiency on IL-13-induced eosinophil recruitment into adult lung airspaces. Eosinophil recruitment into the airspaces was elevated in IL-13-treated WT mice but not in IL-13-treated mye-IL4Rα mice. Consistent with the degree of eosinophilia, the BALF levels of eosinophil recruitment-associated cytokines were significantly elevated in IL-13-treated WT but not in IL-13-treated mye-IL4Rα mice. These data establish that myeloid-IL4Rα is an indispensable component of the IL-33-ILCsIL-13-IL4Rα axis of eosinophil recruitment.

Publication Source (Journal or Book title)

Scientific reports

First Page

15465

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