scholarly journals IL-33–Responsive Lineage−CD25+CD44hi Lymphoid Cells Mediate Innate Type 2 Immunity and Allergic Inflammation in the Lungs

2011 ◽  
Vol 188 (3) ◽  
pp. 1503-1513 ◽  
Author(s):  
Kathleen R. Bartemes ◽  
Koji Iijima ◽  
Takao Kobayashi ◽  
Gail M. Kephart ◽  
Andrew N. McKenzie ◽  
...  
Keyword(s):  
Allergic Inflammation ◽  
Lymphoid Cells ◽  
Type 2 Immunity

scholarly journals Selective deletion of SHIP-1 in hematopoietic cells in mice leads to severe lung inflammation involving ILC2 cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Xujun Ye ◽  
Fengrui Zhang ◽  
Li Zhou ◽  
Yadong Wei ◽  
Li Zhang ◽  
...  
Keyword(s):  
Lung Inflammation ◽  
Airway Remodeling ◽  
Pulmonary Inflammation ◽  
Hematopoietic Cells ◽  
Cell Lineage ◽  
Allergic Inflammation ◽  
Cell Types ◽  
Lymphoid Cells ◽  
Whole Body

AbstractSrc homology 2 domain–containing inositol 5-phosphatase 1 (SHIP-1) regulates the intracellular levels of phosphotidylinositol-3, 4, 5-trisphosphate, a phosphoinositide 3–kinase (PI3K) product. Emerging evidence suggests that the PI3K pathway is involved in allergic inflammation in the lung. Germline or induced whole-body deletion of SHIP-1 in mice led to spontaneous type 2-dominated pulmonary inflammation, demonstrating that SHIP-1 is essential for lung homeostasis. However, the mechanisms by which SHIP-1 regulates lung inflammation and the responsible cell types are still unclear. Deletion of SHIP-1 selectively in B cells, T cells, dendritic cells (DC) or macrophages did not lead to spontaneous allergic inflammation in mice, suggesting that innate immune cells, particularly group 2 innate lymphoid cells (ILC2 cells) may play an important role in this process. We tested this idea using mice with deletion of SHIP-1 in the hematopoietic cell lineage and examined the changes in ILC2 cells. Conditional deletion of SHIP-1 in hematopoietic cells in Tek-Cre/SHIP-1 mice resulted in spontaneous pulmonary inflammation with features of type 2 immune responses and airway remodeling like those seen in mice with global deletion of SHIP-1. Furthermore, when compared to wild-type control mice, Tek-Cre/SHIP-1 mice displayed a significant increase in the number of IL-5/IL-13 producing ILC2 cells in the lung at baseline and after stimulation by allergen Papain. These findings provide some hints that PI3K signaling may play a role in ILC2 cell development at baseline and in response to allergen stimulation. SHIP-1 is required for maintaining lung homeostasis potentially by restraining ILC2 cells and type 2 inflammation.

Neutralization of IL-33 Modifies the Type 2 and Type 3 Inflammatory Signature of Viral Induced Asthma Exacerbation.

2021 ◽  
Author(s):  
Kristi J Warren ◽  
Jill A Poole ◽  
Jenea M Sweeter ◽  
Jane M DeVasure ◽  
John D Dickinson ◽  
...  
Keyword(s):  
Asthma Exacerbation ◽  
Viral Infections ◽  
Immune Cell ◽  
Allergic Inflammation ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Protein Markers ◽  
Mucus Cell ◽  
Rsv Infection

Abstract Background: Respiratory viral infections are one of the leading causes of need for emergency care and hospitalizations in asthmatic individuals, and airway-secreted cytokines are released within hours of viral infection to initiate these exacerbations. IL-33, specifically, contributes to these allergic exacerbations by amplifying type 2 inflammation. We hypothesized that blocking IL-33 in RSV-induced exacerbation would significantly reduce allergic inflammation. Methods: Sensitized BALB/c mice were challenged with aerosolized ovalbumin (OVA) to establish allergic inflammation, followed by RSV-A2 infection to yield four treatment groups: Saline only (Saline), RSV-infected alone (RSV), OVA alone (OVA), and OVA-treated with RSV infection (OVA-RSV). Lung outcomes included lung mRNA and protein markers of allergic inflammation, histology for mucus cell metaplasia and lung immune cell influx by cytospin and flow cytometry. Results: While thymic stromal lymphopoietin (TSLP) and IL-33 were detected 6 hours after RSV infection in the OVA-RSV mice, IL-23 protein was uniquely upregulated in RSV-infected mice alone. OVA-RSV animals varied from RSV- or OVA-treated mice as they had increased lung eosinophils, neutrophils, group 2 innate lymphoid cells (ILC2) and group 3 innate lymphoid cells (ILC3) detectable as early as 6 hours after RSV infection. Neutralized IL-33 significantly reduced ILC2 and eosinophils, and the prototypical allergic proteins, IL-5, IL-13, CCL17 and CCL22 in OVA-RSV mice. Numbers of neutrophils and ILC3 were also reduced with anti-IL-33 treatment in both RSV and OVA-RSV treated animals as well. Conclusions: Taken together, our findings indicate a broad reduction in allergic-proinflammatory events mediated by IL-33 in RSV-induced asthma exacerbation.

scholarly journals Effects of BMP7 produced by group 2 innate lymphoid cells on adipogenesis

2020 ◽  
Vol 32 (6) ◽  
pp. 407-419 ◽  
Author(s):  
Yurina Miyajima ◽  
Kafi N Ealey ◽  
Yasutaka Motomura ◽  
Miho Mochizuki ◽  
Natsuki Takeno ◽  
...  
Keyword(s):  
Lipid Accumulation ◽  
Adipocyte Differentiation ◽  
Allergic Inflammation ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Brown Adipocytes ◽  
Morphogenetic Protein ◽  
Group 2

Abstract Group 2 innate lymphoid cells (ILC2s) are type 2 cytokine-producing cells that have important roles in helminth infection and allergic inflammation. ILC2s are tissue-resident cells, and their phenotypes and roles are regulated by tissue-specific environmental factors. While the role of ILC2s in the lung, intestine and bone marrow has been elucidated in many studies, their role in adipose tissues is still unclear. Here, we report on the role of ILC2-derived bone morphogenetic protein 7 (BMP7) in adipocyte differentiation and lipid accumulation. Co-culture of fat-derived ILC2s with pluripotent mesenchymal C3H10T1/2 cells and committed white preadipocyte 3T3-L1 cells resulted in their differentiation to adipocytes and induced lipid accumulation. Co-culture experiments using BMP7-deficient ILC2s revealed that BMP7, produced by ILC2s, induces differentiation into brown adipocytes. Our results demonstrate that BMP7, produced by ILC2s, affects adipocyte differentiation, particularly in brown adipocytes.

scholarly journals A mechanism for the induction of type 2 immune responses by a protease allergen in the genital tract

2017 ◽  
Vol 114 (7) ◽  
pp. E1188-E1195 ◽  
Author(s):  
Ji Eun Oh ◽  
Dong Sun Oh ◽  
Hi Eun Jung ◽  
Heung Kyu Lee
Keyword(s):  
Immune Responses ◽  
Genital Tract ◽  
Primary Response ◽  
Lymphoid Cells ◽  
Genital Mucosa ◽  
Type 2 Immunity ◽  
Parasite Infections ◽  
Barrier Surface ◽  
External Stimuli

The genital mucosa is a barrier that is constantly exposed to a variety of pathogens, allergens, and external stimuli. Although both allergen exposure and parasite infections frequently occur in the genital area, the mechanism by which immune responses—particularly type 2 immunity—are induced has rarely been studied in the genital mucosa. Here, we demonstrate the induction of T helper type 2 (Th2) immunity in the genital mucosa in response to a model allergen, the protease papain. Intravaginal papain immunization induced type 2 immunity in a manner that was dependent on protease activity and the estrous phase of the mice. In addition, IL-33 was released from the vaginal epithelia after intravaginal papain immunization, leading to the activation of type 2 innate lymphoid cells (ILC2s). Moreover, the IL-33–MyD88 (myeloid differentiation primary response gene 88) signaling pathway was critical for the induction of type 2 immunity. We also found that Th2 differentiation in response to intravaginal papain treatment requires a specific dendritic cell (DC) subset that is controlled by interferon regulatory factor 4 (IRF4). These findings suggest that type 2 immunity is induced by a unique mechanism in the genital tract, which is an important, but often overlooked, barrier surface.

scholarly journals Allergic inflammation is exacerbated by allergen-induced type 2 innate lymphoid cells in a murine model of allergic rhinitis

2017 ◽  
Vol 55 (4) ◽  
pp. 339-347 ◽  
Author(s):  
L. Lin ◽  
F. Dai ◽  
J.J. Wei ◽  
X.Y. Tang ◽  
Z. Chen ◽  
...  
Keyword(s):  
Allergic Rhinitis ◽  
Murine Model ◽  
Allergic Inflammation ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells

scholarly journals Neutralization of IL-33 modifies the type 2 and type 3 inflammatory signature of viral induced asthma exacerbation

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Kristi J. Warren ◽  
Jill A. Poole ◽  
Jenea M. Sweeter ◽  
Jane M. DeVasure ◽  
John D. Dickinson ◽  
...  
Keyword(s):  
Asthma Exacerbation ◽  
Viral Infections ◽  
Immune Cell ◽  
Allergic Inflammation ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Protein Markers ◽  
Mucus Cell ◽  
Rsv Infection

Abstract Background Respiratory viral infections are one of the leading causes of need for emergency care and hospitalizations in asthmatic individuals, and airway-secreted cytokines are released within hours of viral infection to initiate these exacerbations. IL-33, specifically, contributes to these allergic exacerbations by amplifying type 2 inflammation. We hypothesized that blocking IL-33 in RSV-induced exacerbation would significantly reduce allergic inflammation. Methods Sensitized BALB/c mice were challenged with aerosolized ovalbumin (OVA) to establish allergic inflammation, followed by RSV-A2 infection to yield four treatment groups: saline only (Saline), RSV-infected alone (RSV), OVA alone (OVA), and OVA-treated with RSV infection (OVA-RSV). Lung outcomes included lung mRNA and protein markers of allergic inflammation, histology for mucus cell metaplasia and lung immune cell influx by cytospin and flow cytometry. Results While thymic stromal lymphopoietin (TSLP) and IL-33 were detected 6 h after RSV infection in the OVA-RSV mice, IL-23 protein was uniquely upregulated in RSV-infected mice alone. OVA-RSV animals varied from RSV- or OVA-treated mice as they had increased lung eosinophils, neutrophils, group 2 innate lymphoid cells (ILC2) and group 3 innate lymphoid cells (ILC3) detectable as early as 6 h after RSV infection. Neutralized IL-33 significantly reduced ILC2 and eosinophils, and the prototypical allergic proteins, IL-5, IL-13, CCL17 and CCL22 in OVA-RSV mice. Numbers of neutrophils and ILC3 were also reduced with anti-IL-33 treatment in both RSV and OVA-RSV treated animals as well. Conclusions Taken together, our findings indicate a broad reduction in allergic-proinflammatory events mediated by IL-33 neutralization in RSV-induced asthma exacerbation.

scholarly journals DOCK8 deficiency causes a skewing to type 2 immunity in the gut with expansion of group 2 innate lymphoid cells

2021 ◽  
Vol 559 ◽  
pp. 135-140
Author(s):  
Keisuke Matsubara ◽  
Kazufumi Kunimura ◽  
Nana Yamane ◽  
Ryosuke Aihara ◽  
Tetsuya Sakurai ◽  
...  
Keyword(s):  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Type 2 Immunity ◽  
Dock8 Deficiency ◽  
Group 2

scholarly journals Up-regulation of gasdermin C in mouse small intestine is associated with lytic cell death in enterocytes in worm-induced type 2 immunity

2021 ◽  
Vol 118 (30) ◽  
pp. e2026307118
Author(s):  
Ranhui Xi ◽  
Julia Montague ◽  
Xiaoli Lin ◽  
Chanyi Lu ◽  
Weiwei Lei ◽  
...  
Keyword(s):  
Cell Death ◽  
Cell Expansion ◽  
Lymphoid Cells ◽  
Hek293 Cells ◽  
Classical Type ◽  
Wild Type ◽  
Villus Atrophy ◽  
Type 2 Immunity ◽  
Tuft Cell

“Taste-like” tuft cells in the intestine trigger type 2 immunity in response to worm infection. The secretion of interleukin-13 (IL-13) from type 2 innate lymphoid cells (ILC2) represents a key step in the tuft cell–ILC2 cell–intestinal epithelial cell circuit that drives the clearance of worms from the gut via type 2 immune responses. Hallmark features of type 2 responses include tissue remodeling, such as tuft and goblet cell expansion, and villus atrophy, yet it remains unclear if additional molecular changes in the gut epithelium facilitate the clearance of worms from the gut. Using gut organoids, we demonstrated that IL-4 and IL-13, two type 2 cytokines with similar functions, not only induced the classical type 2 responses (e.g., tuft cell expansion) but also drastically up-regulated the expression of gasdermin C genes (Gsdmcs). Using an in vivo worm-induced type 2 immunity model, we confirmed the up-regulation of Gsdmcs in Nippostrongylus brasiliensis–infected wild-type C57BL/6 mice. Consistent with gasdermin family members being principal effectors of pyroptosis, overexpression of Gsdmc2 in human embryonic kidney 293 (HEK293) cells triggered pyroptosis and lytic cell death. Moreover, in intestinal organoids treated with IL-4 or IL-13, or in wild-type mice infected with N. brasiliensis, lytic cell death increased, which may account for villus atrophy observed in worm-infected mice. Thus, we propose that the up-regulated Gsdmc family may be major effectors for type 2 responses in the gut and that Gsdmc-mediated pyroptosis may provide a conduit for the release of antiparasitic factors from enterocytes to facilitate the clearance of worms.

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