Interferon gamma constrains type 2 lymphocyte niche boundaries during mixed inflammation

Cautivo, Kelly M.; Matatia, Peri; Lizama, Carlos O.; Mroz, Nicholas M.; Dahlgren, Madelene W; Yu, Sophie E.; Sbierski-Kind, Julia; Taruselli, Marcela T.; Brooks, Jeremy F.; Wade-Vallance, Adam K.; Caryotakis, Sofia; Chang, Anthony; Liang, Hong-Erh; Zikherman, Julie; Locksley, Richard M.; Molofsky, Ari B.

doi:10.1016/j.immuni.2021.12.014

Cited by 33 publications

(37 citation statements)

References 100 publications

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“…Additional data derived from our BM-ILC2 cultures validate this protocol as a means to generate bona fide ILC2 cells, since our ILC2 populations express both IL-5 and IL-13. In agreement with other works, our data indicate that IL-5 induction is dependent on IL-33 as has been observed in lung-derived ILC2s ( 42 ). Contrastingly, IL-13 expression does not require IL-33, however it is significantly enhanced by the presence of the alarmin.…”

Section: Discussionsupporting

confidence: 93%

IL-33 and the PKA Pathway Regulate ILC2 Populations Expressing IL-9 and ST2

Olguín-Martínez

Muñoz-Paleta²,

Ruiz-Medina³

et al. 2022

Front. Immunol.

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Type 2 Innate lymphoid cells (ILC2s) are tissue-resident immune cells activated by epithelial-derived alarmins upon tissue damage. They regulate immunity against helminth parasites and allergies by expressing type 2 immune response cytokines including IL-9, known to be critical for inducing and potentiating the immune response in such context. Although ILC2s are reported to be the main source of IL-9 in mice during N. brasiliensis infection, the mechanisms that regulate the expression of IL-9 in these cells are yet to be described. Recent studies have shown that in addition to cytokines, multiple molecules can differentially modulate the functions of ILC2s in various contexts both in vitro and in vivo. Among these stimuli are lipid mediators and neuropeptides, which activate the PKA pathway and have been associated with the regulation of type 2 immune cytokines. In this work we found that ILC2s in mice infected with N. brasiliensis can be classified into different groups based on the expression of IL-9 and ST2. These distinct populations were distributed in the lung and the small intestine. Through the development of an in vitro culture system, we sought to determine the stimuli that regulate the expression of these markers in ILC2s. We identified the alarmin IL-33 as being a key player for increased IL-9 expression. Additionally, we found the PKA pathway to be a dual regulator of ILC2 cells, working synergistically with IL-33 to enhance IL-9 production and capable of modulating proliferation and the expression of ILC2 markers. These data provide further evidence of a high heterogeneity between ILC2 subsets in a context dependent manner and calls for careful consideration when choosing the markers to identify these cells in vivo. Distinguishing ILC2 subsets and dissecting their mechanisms of activation is critical for a deeper understanding of the biology of these cells, allowing their manipulation for therapeutic purposes.

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Section: Discussionsupporting

confidence: 93%

IL-33 and the PKA Pathway Regulate ILC2 Populations Expressing IL-9 and ST2

Olguín-Martínez

Muñoz-Paleta²,

Ruiz-Medina³

et al. 2022

Front. Immunol.

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“…Subsequent work in the same group found that upper-airway IL-24, an IL-4-induced epithelial type 2 cytokine, could be used as a proxy for lower-airway IL-24 to diagnose allergic asthma (93). Recently, Cautivo et al proposed a topographic cross-regulation model for Th1 and Th2 cells in the lung, wherein IFN-g production by Th1 cells directly restricts IL-5-producing Th2 cells dispersion and lung parenchymal accumulation (94). The evidence mentioned above supports the original Th1/Th2 paradigm that described a simple framework for our understanding of protective and pathogenetic response in the context of CD4 + T cells in response to the allergen.…”

Section: The Role Of Th1 Cells In Stable Asthmamentioning

confidence: 76%

Distinct spatial and temporal roles for Th1, Th2, and Th17 cells in asthma

Luo

et al. 2022

Front. Immunol.

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Immune response in the asthmatic respiratory tract is mainly driven by CD4+ T helper (Th) cells, represented by Th1, Th2, and Th17 cells, especially Th2 cells. Asthma is a heterogeneous and progressive disease, reflected by distinct phenotypes orchestrated by τh2 or non-Th2 (Th1 and Th17) immune responses at different stages of the disease course. Heterogeneous cytokine expression within the same Th effector state in response to changing conditions in vivo and interlineage relationship among CD4+ T cells shape the complex immune networks of the inflammatory airway, making it difficult to find one panacea for all asthmatics. Here, we review the role of three T helper subsets in the pathogenesis of asthma from different stages, highlighting timing is everything in the immune system. We also discuss the dynamic topography of Th subsets and pathogenetic memory Th cells in asthma.

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“…This positioning allows them to react to environmental cues such as antigens in the airways and limits exposure of alveoli to potentially tissue-damaging inflammatory stimuli. Following inflammatory cues, such as allergic inflammation, ILC2s traffic to the parenchyma, where they mediate effector functions [ 74 ]. Similarly, hepatic ILC2s are located near the vasculature [ 73 ], suggesting that they can not only sense local cues but also respond to systemic changes and signals in the bloodstream.…”

Section: Ilc2s and Ilc3s – Rare But Ready To Reactmentioning

confidence: 99%

The unique role of innate lymphoid cells in cancer and the hepatic microenvironment

Curio

Belz

2022

Cell Mol Immunol

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Cancer is a complex disease, and despite incredible progress over the last decade, it remains the leading cause of death worldwide. Liver cancers, including hepatocellular carcinoma (HCC), and liver metastases are distinct from other cancers in that they typically emerge as a consequence of long-term low-grade inflammation. Understanding the mechanisms that underpin inflammation-driven tissue remodeling of the hepatic immune environment is likely to provide new insights into much needed treatments for this devastating disease. Group 1 innate lymphoid cells (ILCs), which include natural killer (NK) cells and ILC1s, are particularly enriched in the liver and thought to contribute to the pathogenesis of a number of liver diseases, including cancer. NK cells are an attractive, but underexplored, therapeutic target in hepatic disease due to their role in immunosurveillance and their ability to recognize and eliminate malignant cells. ILC1s are closely related to and share many phenotypic features with NK cells but are less well studied. Thus, their utility in immunotherapeutic approaches is not yet well understood. Here, we review our current understanding of ILCs in cancer with a particular focus on liver and liver-related diseases.

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Interferon gamma constrains type 2 lymphocyte niche boundaries during mixed inflammation

Cited by 33 publications

References 100 publications

IL-33 and the PKA Pathway Regulate ILC2 Populations Expressing IL-9 and ST2

IL-33 and the PKA Pathway Regulate ILC2 Populations Expressing IL-9 and ST2

Distinct spatial and temporal roles for Th1, Th2, and Th17 cells in asthma

The unique role of innate lymphoid cells in cancer and the hepatic microenvironment

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