scholarly journals Innate Lymphoid Cell–Dependent Airway Epithelial and Inflammatory Responses to Inhaled Ozone: A New Paradigm in Pathogenesis

2019 ◽  
Vol 47 (8) ◽  
pp. 993-1003 ◽  
Author(s):  
Jack R. Harkema ◽  
James G. Wagner
Keyword(s):  
Inflammatory Responses ◽  
Mucous Cell ◽  
Upper Airway ◽  
Air Pollutant ◽  
Lymphoid Cells ◽  
Laboratory Animals ◽  
New Paradigm ◽  
Type 2 Immunity ◽  
Airway Pathology

Epidemiological associations have been made between the new onset of childhood rhinitis/asthma and exposures to elevated ambient levels of ozone, a commonly encountered gaseous air pollutant. Our laboratory was the first to find that mice repeatedly exposed to ozone develop nasal type 2 immunity and eosinophilic rhinitis with mucous cell metaplasia. More recently, we have found that these ozone-induced upper airway alterations are mediated by group 2 innate lymphoid cells (ILC2s) and not by T and B cells that are important in adaptive immune responses typically associated with allergic rhinitis and asthma. Furthermore, repeated exposures of mice to ozone cause ILC2-mediated type 2 immunity and airway pathology in the lungs, like those found in the nasal airways. Our recent findings in ozone-exposed mice complement and extend previous reports of nonallergic nasal airway disease in ozone-exposed rats and nonhuman primates. Overall, these experimental results in laboratory animals suggest a plausible ILC2-dependent paradigm for the toxicologic pathobiology that underlies the development of nonallergic rhinitis/asthma in children who live in environments with repeated occurrences of high ambient concentrations of ozone.

scholarly journals Innate Lymphoid Cells Mediate Pulmonary Eosinophilic Inflammation, Airway Mucous Cell Metaplasia, and Type 2 Immunity in Mice Exposed to Ozone

2017 ◽  
Vol 45 (6) ◽  
pp. 692-704 ◽  
Author(s):  
Kazuyoshi Kumagai ◽  
Ryan P. Lewandowski ◽  
Daven N. Jackson-Humbles ◽  
Nicholas Buglak ◽  
Ning Li ◽  
...  
Keyword(s):  
Mucous Cell ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Eosinophilic Inflammation ◽  
Type 2 Immunity

scholarly journals Group 2 Innate Lymphoid Cells: Central Players in a Recurring Theme of Repair and Regeneration

2020 ◽  
Vol 21 (4) ◽  
pp. 1350 ◽  
Author(s):  
Melina Messing ◽  
Sia Cecilia Jan-Abu ◽  
Kelly McNagny
Keyword(s):  
T Regulatory Cells ◽  
Inflammatory Responses ◽  
Expression Profiles ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Helminth Infections ◽  
Neonatal Immunity ◽  
Group 2 ◽  
Transcription Factor Expression

Innate lymphoid cells (ILCs) are recently discovered innate counterparts to the well-established T helper cell subsets and are most abundant at barrier surfaces, where they participate in tissue homeostasis and inflammatory responses against invading pathogens. Group 2 innate lymphoid cells (ILC2s) share cytokine and transcription factor expression profiles with type-2 helper T cells and are primarily associated with immune responses against allergens and helminth infections. Emerging data, however, suggests that ILC2s are also key regulators in other inflammatory settings; both in a beneficial context, such as the establishment of neonatal immunity, tissue repair, and homeostasis, and in the context of pathological tissue damage and disease, such as fibrosis development. This review focuses on the interactions of ILC2s with stromal cells, eosinophils, macrophages, and T regulatory cells that are common to the different settings in which type-2 immunity has been explored. We further discuss how an understanding of these interactions can reveal new avenues of therapeutic tissue regeneration, where the role of ILC2s is yet to be fully established.

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 Strain Differences in a Murine Model of Air Pollutant–induced Nonatopic Asthma and Rhinitis

2016 ◽  
Vol 45 (1) ◽  
pp. 161-171 ◽  
Author(s):  
Jack R. Harkema ◽  
Lucas A. Hotchkiss ◽  
Nicholas A. Vetter ◽  
Daven N. Jackson-Humbles ◽  
Ryan P. Lewandowski ◽  
...  
Keyword(s):  
Genetic Factors ◽  
Mucous Cell ◽  
Strain Differences ◽  
Air Pollutant ◽  
Similar Degree ◽  
Eosinophilic Inflammation ◽  
Expression Of Genes ◽  
Pulmonary Airways ◽  
Strain Dependent

Ozone is an irritating gas found in photochemical smog. Epidemiological associations have been made between the onset of asthma and childhood exposures to increasing levels of ambient ozone (i.e., air pollutant–induced nonatopic asthma). Individuals, however, vary in their susceptibility to this outdoor air pollutant, which may be due, in part, to their genetic makeup. The present study was designed to test the hypothesis that there are murine strain-dependent differences in pulmonary and nasal pathologic responses to repeated ozone exposures. C57BL/6NTac and BALB/cNTac mice were exposed to 0 or 0.8 ppm ozone, 4 hr/day, for 9 consecutive weekdays. In both strains of mice, ozone induced eosinophilic inflammation and mucous cell metaplasia in the nasal and pulmonary airways. Lungs of ozone-exposed C57BL/6NTac mice, however, had greater eosinophilic inflammation, mucous cell metaplasia, and expression of genes related to type 2 immunity and airway mucus hypersecretion, as compared to similarly exposed BALB/cNTac mice. Ozone-exposed C57BL/6NTac mice also had greater eosinophilic rhinitis but a similar degree of mucous cell metaplasia in nasal epithelium, as ozone-exposed BALB/cNTac mice. These findings suggest that nonatopic individuals may differ in their inflammatory and epithelial responses to repeated ozone exposures that are due, in part, to genetic factors.

scholarly journals Androgen signaling negatively controls group 2 innate lymphoid cells

2017 ◽  
Vol 214 (6) ◽  
pp. 1581-1592 ◽  
Author(s):  
Sophie Laffont ◽  
Eve Blanquart ◽  
Magali Savignac ◽  
Claire Cénac ◽  
Gilles Laverny ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Lung Inflammation ◽  
Inflammatory Responses ◽  
Allergic Airway Inflammation ◽  
Innate Lymphoid Cells ◽  
Protective Role ◽  
Lymphoid Cells ◽  
Peripheral Tissues ◽  
Group 2

Prevalence of asthma is higher in women than in men, but the mechanisms underlying this sex bias are unknown. Group 2 innate lymphoid cells (ILC2s) are key regulators of type 2 inflammatory responses. Here, we show that ILC2 development is greatly influenced by male sex hormones. Male mice have reduced numbers of ILC2 progenitors (ILC2Ps) and mature ILC2s in peripheral tissues compared with females. In consequence, males exhibit reduced susceptibility to allergic airway inflammation in response to environmental allergens and less severe IL-33–driven lung inflammation, correlating with an impaired expansion of lung ILC2s. Importantly, orchiectomy, but not ovariectomy, abolishes the sex differences in ILC2 development and restores IL-33–mediated lung inflammation. ILC2Ps express the androgen receptor (AR), and AR signaling inhibits their differentiation into mature ILC2s. Finally, we show that hematopoietic AR expression limits IL-33–driven lung inflammation through a cell-intrinsic inhibition of ILC2 expansion. Thus, androgens play a crucial protective role in type 2 airway inflammation by negatively regulating ILC2 homeostasis, thereby limiting their capacity to expand locally in response to IL-33.

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 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.

scholarly journals A Gata3 enhancer necessary for ILC2 development and function

2021 ◽  
Vol 118 (32) ◽  
pp. e2106311118
Author(s):  
Darshan N. Kasal ◽  
Zhitao Liang ◽  
Maile K. Hollinger ◽  
Crystal Y. O’Leary ◽  
Wioletta Lisicka ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Lymphoid Cells ◽  
Th2 Cells ◽  
Regulatory Pathways ◽  
Th2 Cell ◽  
Gata3 Expression ◽  
Gene Regulatory ◽  
High Level ◽  
And Function

The type 2 helper effector program is driven by the master transcription factor GATA3 and can be expressed by subsets of both innate lymphoid cells (ILCs) and adaptive CD4+ T helper (Th) cells. While ILC2s and Th2 cells acquire their type 2 differentiation program under very different contexts, the distinct regulatory mechanisms governing this common program are only partially understood. Here we show that the differentiation of ILC2s, and their concomitant high level of GATA3 expression, are controlled by a Gata3 enhancer, Gata3 +674/762, that plays only a minimal role in Th2 cell differentiation. Mice lacking this enhancer exhibited defects in several but not all type 2 inflammatory responses, depending on the respective degree of ILC2 and Th2 cell involvement. Our study provides molecular insights into the different gene regulatory pathways leading to the acquisition of the GATA3-driven type 2 helper effector program in innate and adaptive lymphocytes.

Sign in / Sign up

Export Citation Format

Share Document