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Review
. 2022 Jun 9:13:918458.
doi: 10.3389/fimmu.2022.918458. eCollection 2022.

Heterogeneity of ILC2s in the Lungs

Masato Asaoka  1 , Hiroki Kabata  1 , Koichi Fukunaga  1
Affiliations
Review

Heterogeneity of ILC2s in the Lungs

Masato Asaoka et al. Front Immunol. .

Abstract

Group 2 innate lymphoid cells (ILC2s) are GATA3-expressing type 2 cytokine-producing innate lymphocytes that are present in various organs throughout the body. Basically, ILC2s are tissue-resident cells associated with a variety of pathological conditions in each tissue. Differences in the tissue-specific properties of ILC2s are formed by the post-natal tissue environment; however, diversity exists among ILC2s within each localized tissue due to developmental timing and activation. Diversity between steady-state and activated ILC2s in mice and humans has been gradually clarified with the advancement of single-cell RNA-seq technology. Another layer of complexity is that ILC2s can acquire other ILC-like functions, depending on their tissue environment. Further, ILC2s with immunological memory and exhausted ILC2s are both present in tissues, and the nature of ILC2s varies with senescence. To clarify how ILC2s affect human diseases, research should be conducted with a comprehensive understanding of ILC2s, taking into consideration the diversity of ILC2s rather than a snapshot of a single section. In this review, we summarize the current understanding of the heterogeneity of ILC2s in the lungs and highlight a novel field of immunology.

Keywords: aging; development; group 2 innate lymphoid cells; heterogeneity; memory; plasticity.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Heterogeneity of lung group 2 innate lymphoid cells (ILC2s) in mice at steady state. Lung ILC2s have increased expression of Il1rl1, while intestinal ILC2s highly express Il17rb, Ahr and Nmur1, and Il18r1 is enriched in skin ILC2s, respectively. Adult ILC2s in the lung have three developmental origins: prenatal, neonatal, and adult origin. The lung resident-ILC2 progenitor cells differentiate into at least three subtypes of mature ILC2s. This figure is created based on ref (27, 32, 41).
Figure 2
Figure 2
Heterogeneity of lung group 2 innate lymphoid cells (ILC2s) during N.brasiliensis infection. Time course of activation of lung ILC2s in the lungs following a helminth infection. High levels of Il5 high natural ILC2s that appear shortly after the infection. Then, iILC2 populations transiently increased, and Il13 high natural ILC2 populations increased thereafter. iILC2, inflammatory type 2 innate lymphoid cell; nILC2, natural type 2 innate lymphoid cell; N. brasiliensis, Nippostrongylus brasiliensis.
Figure 3
Figure 3
Overview of plasticity and trained lung group 2 innate lymphoid cells (ILC2) in the lung.
See this image and copyright information in PMC

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