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

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 consis...

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Autores principales:	Sonika Patial, Brandon W. Lewis, Thao Vo, Ishita Choudhary, Kshitiz Paudel, Yun Mao, Dhruthi Singamsetty, Frank Brombacher, Yogesh Saini
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/bf37f5aa6f554468883adc4d66eedd11
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spelling	oai:doaj.org-article:bf37f5aa6f554468883adc4d66eedd112021-12-02T18:47:08ZMyeloid-IL4Rα is an indispensable link in IL-33-ILCs-IL-13-IL4Rα axis of eosinophil recruitment in murine lungs10.1038/s41598-021-94843-92045-2322https://doaj.org/article/bf37f5aa6f554468883adc4d66eedd112021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-94843-9https://doaj.org/toc/2045-2322Abstract 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.Sonika PatialBrandon W. LewisThao VoIshita ChoudharyKshitiz PaudelYun MaoDhruthi SingamsettyFrank BrombacherYogesh SainiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sonika Patial Brandon W. Lewis Thao Vo Ishita Choudhary Kshitiz Paudel Yun Mao Dhruthi Singamsetty Frank Brombacher Yogesh Saini Myeloid-IL4Rα is an indispensable link in IL-33-ILCs-IL-13-IL4Rα axis of eosinophil recruitment in murine lungs
description	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.
format	article
author	Sonika Patial Brandon W. Lewis Thao Vo Ishita Choudhary Kshitiz Paudel Yun Mao Dhruthi Singamsetty Frank Brombacher Yogesh Saini
author_facet	Sonika Patial Brandon W. Lewis Thao Vo Ishita Choudhary Kshitiz Paudel Yun Mao Dhruthi Singamsetty Frank Brombacher Yogesh Saini
author_sort	Sonika Patial
title	Myeloid-IL4Rα is an indispensable link in IL-33-ILCs-IL-13-IL4Rα axis of eosinophil recruitment in murine lungs
title_short	Myeloid-IL4Rα is an indispensable link in IL-33-ILCs-IL-13-IL4Rα axis of eosinophil recruitment in murine lungs
title_full	Myeloid-IL4Rα is an indispensable link in IL-33-ILCs-IL-13-IL4Rα axis of eosinophil recruitment in murine lungs
title_fullStr	Myeloid-IL4Rα is an indispensable link in IL-33-ILCs-IL-13-IL4Rα axis of eosinophil recruitment in murine lungs
title_full_unstemmed	Myeloid-IL4Rα is an indispensable link in IL-33-ILCs-IL-13-IL4Rα axis of eosinophil recruitment in murine lungs
title_sort	myeloid-il4rα is an indispensable link in il-33-ilcs-il-13-il4rα axis of eosinophil recruitment in murine lungs
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/bf37f5aa6f554468883adc4d66eedd11
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Myeloid-IL4Rα is an indispensable link in IL-33-ILCs-IL-13-IL4Rα axis of eosinophil recruitment in murine lungs

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