Group 2 Innate Lymphoid Cells Directly Induce B Cell Activation in Humans

Type 2 immunity helps protect the host from infection, but it also plays key roles in tissue homeostasis, metabolism, and repair. Unfortunately, inappropriate type 2 immune reactions may lead to allergy and asthma. Group 2 innate lymphoid cells (ILC2s) in the lungs respond rapidly to local environmental cues, such as the release of epithelium-derived type 2 initiator cytokines/alarmins, producing type 2 effector cytokines such as IL-4, IL-5, and IL-13 in response to tissue damage and infection. ILC2s are associated with the severity of allergic asthma, and experimental models of lung inflammation have shown how they act as playmakers, receiving signals variously from stromal and immune cells as well as the nervous system and then disseminating cytokine cues to elicit effector functions and potentiate CD4+ T helper cell activation, both of which characterize the pathology of allergic asthma. Recent breakthroughs identifying stromal- and neuronal-derived microenvironmental cues that regulate ILC2s, along with studies recognizing the potential plasticity of ILC2s, have improved our understanding of the immunoregulation of asthma and opened new avenues for drug discovery. Expected final online publication date for the Annual Review of Immunology, Volume 39 is April 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

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Influx, Persistence, and Recall of Eosinophils and GATA-3+ Innate Lymphoid Cells in the Nasal Mucosa of Mice Exposed and Reexposed to the Gaseous Air Pollutant Ozone

Toxicologic Pathology ◽

10.1177/0192623319882768 ◽

2019 ◽

Vol 48 (2) ◽

pp. 323-337

Author(s):

Jack R. Harkema ◽

Elyse A. Eldridge ◽

Ryan P. Lewandowski ◽

James G. Wagner

Keyword(s):

B Cell ◽

Messenger Rna ◽

Innate Lymphoid Cells ◽

Air Pollutant ◽

Lymphoid Cells ◽

Ozone Exposure ◽

Nasal Tissue ◽

New Findings ◽

Group 2 ◽

Deficient Mice

Mice exposed to the air pollutant ozone develop eosinophilic rhinitis that is mediated by group 2, GATA-3+, innate lymphoid cells (ILC2s). In the present study, we determined the influx, persistence, and recall of nasal ILC2s and eosinophils in ozone-exposed mice. C57BL/6 (T/B cell sufficient, ILC sufficient), Rag2−/− (T/B cell deficient, ILC sufficient), and Rag2−/−Il2rg−/− (T/B cell deficient, ILC deficient) mice were exposed to 0 or 0.8 ppm ozone for 1 or 9 weekdays and killed 1 or 17 days postexposure. GATA-3+ lymphocytes were sparse in nasal tissue of air-exposed ILC-sufficient mice and absent in ILC-deficient mice. Nine-day, but not 1-day, ozone exposures induced nasal influxes of eosinophils and GATA-3+ lymphocytes in C57BL/6 and Rag2−/− mice but not in Rag2−/−Il2rg−/− mice. Eosinophils waned 17 days postexposure in ILC-sufficient strains of mice. GATA-3+ lymphocytes in C57BL/6 mice also attenuated after exposure but not in ILC-sufficient Rag2−/− mice. Eosinophils, but not GATA-3+ cells, increased rapidly with reexposure in ILC-sufficient mice. Type 2 immune-related messenger RNA expression correlated with cellular responses to ozone. These new findings in mice further elucidate the role of ILC2s in ozone-induced eosinophilic rhinitis and support epidemiologic associations between ozone exposure and eosinophilic inflammation in children.

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Analysis of the activation of lymphoid cells by mitogens in vitro with limiting dilution methods: Adherent peritoneal cells suppress B-cell activation and synergize with WEHI-3 in the activation of T cells by con A

Cellular Immunology ◽

10.1016/0008-8749(86)90256-x ◽

1986 ◽

Vol 99 (2) ◽

pp. 489-499 ◽

Cited By ~ 4

Author(s):

J. Kettman ◽

A. Soederberg ◽

I. Lefkovits

Keyword(s):

T Cells ◽

B Cell ◽

Cell Activation ◽

Lymphoid Cells ◽

B Cell Activation ◽

Con A ◽

Peritoneal Cells ◽

Limiting Dilution

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Group 2 innate lymphoid cells support hematopoietic recovery under stress conditions

Journal of Experimental Medicine ◽

10.1084/jem.20200817 ◽

2021 ◽

Vol 218 (5) ◽

Author(s):

Takao Sudo ◽

Yasutaka Motomura ◽

Daisuke Okuzaki ◽

Tetsuo Hasegawa ◽

Takafumi Yokota ◽

...

Keyword(s):

B Cell ◽

Innate Lymphoid Cells ◽

Lymphoid Cells ◽

Stress Conditions ◽

Hematopoietic Stem ◽

Gm Csf ◽

Induced Stress ◽

Hematopoietic Recovery ◽

Group 2 ◽

Resident Group

The cell-cycle status of hematopoietic stem and progenitor cells (HSPCs) becomes activated following chemotherapy-induced stress, promoting bone marrow (BM) regeneration; however, the underlying molecular mechanism remains elusive. Here we show that BM-resident group 2 innate lymphoid cells (ILC2s) support the recovery of HSPCs from 5-fluorouracil (5-FU)–induced stress by secreting granulocyte-macrophage colony-stimulating factor (GM-CSF). Mechanistically, IL-33 released from chemo-sensitive B cell progenitors activates MyD88-mediated secretion of GM-CSF in ILC2, suggesting the existence of a B cell–ILC2 axis for maintaining hematopoietic homeostasis. GM-CSF knockout mice treated with 5-FU showed severe loss of myeloid lineage cells, causing lethality, which was rescued by transferring BM ILC2s from wild-type mice. Further, the adoptive transfer of ILC2s to 5-FU–treated mice accelerates hematopoietic recovery, while the reduction of ILC2s results in the opposite effect. Thus, ILC2s may function by “sensing” the damaged BM spaces and subsequently support hematopoietic recovery under stress conditions.

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