Bone marrow type 2 innate lymphoid cells: a local source of interleukin‐5 in interleukin‐33‐driven eosinophilia

Johansson, Karin; Malmhäll, Carina; Ramos‐Ramírez, Patricia; Rådinger, Madeleine

doi:10.1111/imm.12842

Cited by 29 publications

(35 citation statements)

References 51 publications

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“…Our observation that IL-33 can drive IL-5 and CCL24 expression is also supported by another study describing that in eosinophilia of airway inflammation, IL-33stimulated production of IL-5 is accompanied by increased levels of CCL24, but not of CCL11. 47 Despite several reports highlighting the influence of eosinophils on the nature of immune cell infiltrates in various solid tumor models, 12,25,48,49 we observed that IL-33-induced changes in the microenvironment of the CT26 tumors only occurred in CD4 + T cells and Tregs but not M1 macrophages, myeloid derived suppressor cells (MDSCs), CD8 + T or NK cells. In accordance with other studies, 18,19 Tregs slightly increased in CT26 tumors post-IL-33 treatment but this increase was not associated with a higher tumor burden.…”

Section: Discussioncontrasting

confidence: 55%

IL-33 reduces tumor growth in models of colorectal cancer with the help of eosinophils

et al. 2020

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In many types of cancer, presence of eosinophils in tumors correlate with an improved disease outcome. In line with this, activated eosinophils have been shown to reduce tumor growth in colorectal cancer (CRC). Interleukin (IL)-33 has recently emerged as a cytokine that is able to inhibit the development of tumors through eosinophils and other cells of the tumor microenvironment thereby positively influencing disease progress. Here, we asked whether eosinophils are involved in the effects of IL-33 on tumor growth in CRC. In models of CT26 cell engraftment and colitis-associated CRC, tumor growth was reduced after IL-33 treatment. The growth reduction was absent in eosinophil-deficient ΔdblGATA-1 mice but was restored by adoptive transfer of ex vivo-activated eosinophils indicating that the antitumor effect of IL-33 depends on the presence of eosinophils. In vitro, IL-33 increased the expression of markers of activation and homing in eosinophils, such as CD11b and Siglec-F, and the degranulation markers CD63 and CD107a. Increased expression of Siglec-F, CD11b and CD107a was also seen in vivo in eosinophils after IL-33 treatment. Viability and cytotoxic potential of eosinophils and their migration properties toward CCL24 were enhanced indicating direct effects of IL-33 on eosinophils. IL-33 treatment led to increased levels of IL-5 and CCL24 in tumors. Our data show that the presence of eosinophils is mandatory for IL-33-induced tumor reduction in models of CRC and that the mechanisms include eosinophil recruitment, activation and degranulation. Our findings also emphasize the potential use of IL-33 as an adjuvants in CRC immunotherapy.

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Section: Discussioncontrasting

confidence: 55%

IL-33 reduces tumor growth in models of colorectal cancer with the help of eosinophils

et al. 2020

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“…Knockout mice for IL-7Ra or the common γ chain cytokine receptor lack mature ILC2s 61 indicating an important role for IL-7 in generating ILC2s in vivo. Both IL-2 and IL-7 have also been reported to help maintain ILC2 survival 13,61 while culture in combination of IL-2 and IL-7 has been used to maintain ILC2s isolated from lung or Lin −ve ILC progenitors from bone marrow 62,63 . Mesenteric fat ILC2s maintained a Lin −ve /CD45 +ve / Sca1 +ve /KLRG1 +ve phenotype characteristic of ILC2s during culture.…”

Section: Discussionmentioning

confidence: 99%

p38 MAPK signalling regulates cytokine production in IL-33 stimulated Type 2 Innate Lymphoid cells

Petrova

Pesic

Pardali

et al. 2020

Sci Rep

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Type 2 Innate lymphoid cells (ILC2s) are implicated in helminth infections and asthma where they play a role in the production of Th2-type cytokines. ILC2s express the IL-33 receptor and are a major cell type thought to mediate the effects of this cytokine in vivo. To study the signalling pathways that mediate IL-33 induced cytokine production, a culture system was set up to obtain pure populations of ILC2s from mice. Inhibitors of the p38α/β and ERK1/2 MAPK pathways reduced the production of IL-5, IL-6, IL-9, IL-13 and GM-CSF by ILC2 in response to IL-33, with inhibition of p38 having the greatest effect. MK2 and 3 are kinases activated by p38α; MK2/3 inhibitors or knockout of MK2/3 in mice reduced the production of IL-6 and IL-13 (two cytokines implicated in asthma) but not IL-5, IL-9 or GM-CSF in response to IL-33. MK2/3 inhibition also suppressed IL-6 and IL-13 production by human ILC2s. MK2/3 were required for maximal S6 phosphorylation, suggesting an input from the p38α-MK2/3 pathway to mTOR1 activation in ILC2s. The mTORC1 inhibitor rapamycin also reduced IL-6 and IL-13 production, which would be consistent with a model in which MK2/3 regulate IL-6 and IL-13 via mTORC1 activation in ILC2s.Innate lymphoid cells (ILCs) are a recently identified group of lymphocytes acting within the innate immune system. ILCs lack antigen specific receptors, however in terms of the cytokines they produce they mimic various Th cell subsets. ILCs are found in both lymphoid and non-lymphoid tissues, particularly at the barrier sites including skin, respiratory and gastrointestinal systems 1-4 . Based on their effector function, cell surface markers and the transcription factors required for their development, ILCs can be subdivided into several distinct groups 1,2 . Group 1 includes NK cells and ILC1 cells, which are involved in protective immunity to viral infections and antimicrobial responses. The second group comprises of type 2 innate lymphoid cells (ILC2). ILC2 cells secrete type two cytokines and are implicated in responses to helminth infection, asthma and atopic diseases. The third group includes the lymphoid tissue inducer cells and ILC3. In 2017, a potential new group of ILC with regulatory functions was discovered. ILCreg are found in human and mouse gut and limit the activity of ILC1 and ILC3 by secreting the anti-inflammatory cytokine IL-10 5 .The first evidence for the existence of ILC2 cells was found in 2006 when Fallon et al. showed that during infection with the helminth Nippostrongylus brasilienis a population of non-T and non-B cells secrete IL-4, IL-5 and IL-13 and promote helminth expulsion 6 . In 2010, several labs reported the characterisation of ILC2s as a distinct population of cells, which were initially referred to as either neuocytes, innate helper 2 cells or natural helper cells 7-9 . ILC2s are found in the lymphoid tissues such as spleen and mesenteric lymph nodes, as well as in some non-lymphoid organs including fat associated lymphoid clusters, lungs, skin and liver. In mice, ILC2 are character...

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“…In addition, eosinophils released eosinophil peroxidase, which caused oxidative damage to alveolar cells [2]. Th2 cells also released excessive IL-5, which induced bone marrow cells to differentiate to mature eosinophils [42,44]. In patients with asthma, tracheal epithelial cells release high amounts of eotaxin, which induces eosinophil migration and infiltration into the lungs [45].…”

Section: Discussionmentioning

confidence: 99%

Sesamol Alleviates Airway Hyperresponsiveness and Oxidative Stress in Asthmatic Mice

Liou

Chen

et al. 2020

Antioxidants

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Sesamol, isolated from sesame seeds (Sesamum indicum), was previously shown to have antioxidative, anti-inflammatory, and anti-tumor effects. Sesamol also inhibited lipopolysaccharide (LPS)-induced pulmonary inflammatory response in rats. However, it remains unclear how sesamol regulates airway inflammation and oxidative stress in asthmatic mice. This study aimed to investigate the efficacy of sesamol on oxidative stress and airway inflammation in asthmatic mice and tracheal epithelial cells. BALB/c mice were sensitized with ovalbumin, and received oral sesamol on days 14 to 27. Furthermore, BEAS-2B human bronchial epithelial cells were treated with sesamol to investigate inflammatory cytokine levels and oxidative responses in vitro. Our results demonstrated that oral sesamol administration significantly suppressed eosinophil infiltration in the lung, airway hyperresponsiveness, and T helper 2 cell-associated (Th2) cytokine expressions in bronchoalveolar lavage fluid and the lungs. Sesamol also significantly increased glutathione expression and reduced malondialdehyde levels in the lungs of asthmatic mice. We also found that sesamol significantly reduced proinflammatory cytokine levels and eotaxin in inflammatory BEAS-2B cells. Moreover, sesamol alleviated reactive oxygen species formation, and suppressed intercellular cell adhesion molecule-1 (ICAM-1) expression, which reduced monocyte cell adherence. We demonstrated that sesamol showed potential as a therapeutic agent for improving asthma.

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Bone marrow type 2 innate lymphoid cells: a local source of interleukin‐5 in interleukin‐33‐driven eosinophilia

Cited by 29 publications

References 51 publications

IL-33 reduces tumor growth in models of colorectal cancer with the help of eosinophils

IL-33 reduces tumor growth in models of colorectal cancer with the help of eosinophils

p38 MAPK signalling regulates cytokine production in IL-33 stimulated Type 2 Innate Lymphoid cells

Sesamol Alleviates Airway Hyperresponsiveness and Oxidative Stress in Asthmatic Mice

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