The group 2 innate lymphoid cell (<scp>ILC</scp>2) regulatory network and its underlying mechanisms

Kabata, Hiroki; Moro, Kazuyo; Koyasu, Shigeo

doi:10.1111/imr.12706

Cited by 215 publications

(203 citation statements)

References 138 publications

(229 reference statements)

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“…Like T-cells, ILCs have also been categorized according to cytokine production profile (90), of which ILC2 is the most investigated subset in the context of influenza. ILC2 is classically known to produce IL-5 and IL-13 in response to epithelial cytokines IL-25, IL-33, and TSLP (91). Infection of wild type as well as Rag1 −/− mice with IAV led to ILC accumulation in the lung (92) although there is no direct evidence that IAV-mediated ILC accumulation is dependent on AEC-derived cytokines.…”

Section: Epithelial-resident Leukocyte Crosstalk During Early Iav Infmentioning

confidence: 99%

Respiratory Barrier as a Safeguard and Regulator of Defense Against Influenza A Virus and Streptococcus pneumoniae

et al. 2020

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The primary function of the respiratory system of gas exchange renders it vulnerable to environmental pathogens that circulate in the air. Physical and cellular barriers of the respiratory tract mucosal surface utilize a variety of strategies to obstruct microbe entry. Physical barrier defenses including the surface fluid replete with antimicrobials, neutralizing immunoglobulins, mucus, and the epithelial cell layer with rapidly beating cilia form a near impenetrable wall that separates the external environment from the internal soft tissue of the host. Resident leukocytes, primarily of the innate immune branch, also maintain airway integrity by constant surveillance and the maintenance of homeostasis through the release of cytokines and growth factors. Unfortunately, pathogens such as influenza virus and Streptococcus pneumoniae require hosts for their replication and dissemination, and prey on the respiratory tract as an ideal environment causing severe damage to the host during their invasion. In this review, we outline the host-pathogen interactions during influenza and post-influenza bacterial pneumonia with a focus on interand intra-cellular crosstalk important in pulmonary immune responses.

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Section: Epithelial-resident Leukocyte Crosstalk During Early Iav Infmentioning

confidence: 99%

Respiratory Barrier as a Safeguard and Regulator of Defense Against Influenza A Virus and Streptococcus pneumoniae

et al. 2020

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“…While described as lineage marker-negative (Lin À ) cells, ILC2s express various cell surface markers such as c-Kit (CD117), Sca1 (Ly6a), KLRG1, ICOS, and IL-7Ra (CD127) (Mattner and Wirtz, 2017;Moro et al, 2010Moro et al, , 2016. ILC2s respond to the alarmin cytokines interleukin (IL)-33, IL-25, and thymic stromal lymphopoietin (TSLP, combined with IL-33) in addition to eicosanoids such as prostaglandin D2 and leukotriene D4, neuropeptides including neuromedin U, and sex hormones (Kabata et al, 2018). Following activation, they rapidly expand and produce cytokines such as IL-4, IL-5, IL-9, IL-13, and/or amphiregulin Neill et al, 2010;Price et al, 2010;Kabata et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Tumor-Derived Lactic Acid Contributes to the Paucity of Intratumoral ILC2s

et al. 2020

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Graphical AbstractHighlights d ILC2s are involved in eosinophil-associated antitumor responses in melanoma d Lactic acid inhibits function and decreases survival of ILC2s d Tumors with decreased lactic acid production exhibit increased infiltration of ILC2s SUMMARY Group 2 innate lymphoid cells (ILC2s) are abundant in non-lymphoid tissues and increase following infectious and inflammatory insults. In solid tumors, however, ILC2s constitute a relatively small proportion of immune cells. Here, we show, using melanoma as a model, that while the IL-33/IL C2/eosinophil axis suppresses tumor growth, tumor-derived lactate attenuates the function and survival of ILC2s. Melanomas with reduced lactate production (LDHA low ) are growth delayed and typified by an increased number of ILC2s compared with control tumors. Upon IL-33 stimulation, ILC2s accompanied by eosinophils more effectively restrain the growth of LDHA low tumors than control melanomas. Furthermore, database analysis reveals a negative correlation between the expression of LDHA and markers associated with ILC2s and the association of high expression of IL33 and an eosinophil marker SIGLEC8 with better overall survival in human cutaneous melanoma patients. This work demonstrates that the balance between the IL-33/ILC2/eosinophil axis and lactate production by tumor cells regulates melanoma growth.

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“…11), suggesting that this cell population contains a subpopulation which is very important for type 2 immunity. Based on comparison with mammalian studies, and recent indications for the existence of such cells in fish (58), we suspect that these cells are similar to mammalian type 2 innate lymphoid cells (ILC2) which are specifically dedicated to type 2 immunity [reviewed in (94)]. Meanwhile, after stimulation with trout IL-15-RLI, the trout CD4 -CD8 -IgMsplenocytes upregulated IFN and perforin (Fig.…”

Section: Discussionmentioning

confidence: 86%

The first functional characterization of ancient interleukin-15-like (IL-15L) reveals shared and distinct functions of the IL-2, -15 and -15L family cytokines

Yamaguchi

Karger

Keller

et al. 2019

Preprint

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The ancient cytokine interleukin 15-like (IL-15L) was lost in humans and mice but not throughout mammals. This is the first study to describe IL-15L functions, namely in the fish rainbow trout.Fish have only one -chain receptor gene IL-15R, whereas in mammalian evolution this gene duplicated and evolved into IL-15R plus IL-2R. Trout IL-2, IL-15 and IL-15L all could bind IL-15R and were able to induce phosphorylation of transcription factor STAT5. Reminiscent of the mammalian situation, trout IL-15 was more dependent on "in trans" presentation by IL-15R than IL-2. However, whereas trout IL-15 could also function as a free cytokine as known for mammalian IL-15, trout IL-15L function showed a total dependency on in trans presentation by IL-15R. Trout lymphocytes from the mucosal tissues gill and intestine were sensitive to IL-15, but refractory to IL-2 and IL-15L, which is reminiscent of sensitivities to IL-15 in mammals.Distinguishing engagement of the IL-2R/IL-15R receptor chain may explain why IL-2 and IL-15 were selected in evolution as major growth factors for regulatory T cells and lymphocytes in mucosal tissues, respectively. Trout IL-15L efficiently induced expression of IL-4 and IL-13 homologues in CD4 -CD8 -IgMsplenocytes, and we speculate that the responsive cells within that population were type 2 innate lymphoid cells (ILC2). In contrast, trout IL-15 efficiently induced expression of interferon  and perforin in CD4 -CD8 -IgMsplenocytes, and we speculate that in this case the responsive cells were natural killer (NK) cells. In fish, in apparent absence of IL-25, IL-33 and TSLP, primitive IL-15L may have an important role early in the type 2 immunity cytokine cascade. Among trout thymocytes, only CD4 -CD8thymocytes were sensitive to IL-15L, and different than in mammals the CD4 + CD8 + thymocytes were quite sensitive to IL-2. In addition, the present study provides (i) the first molecular evidence for inter-species cytokine with receptor chain interaction across fish-mammal borders, and (ii) suggestive evidence for a tendency of IL-

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The group 2 innate lymphoid cell (ILC2) regulatory network and its underlying mechanisms

Cited by 215 publications

References 138 publications

Respiratory Barrier as a Safeguard and Regulator of Defense Against Influenza A Virus and Streptococcus pneumoniae

Respiratory Barrier as a Safeguard and Regulator of Defense Against Influenza A Virus and Streptococcus pneumoniae

Tumor-Derived Lactic Acid Contributes to the Paucity of Intratumoral ILC2s

The first functional characterization of ancient interleukin-15-like (IL-15L) reveals shared and distinct functions of the IL-2, -15 and -15L family cytokines

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