scholarly journals Maintenance of Type 2 Response by CXCR6-Deficient ILC2 in Papain-Induced Lung Inflammation

2019 ◽  
Vol 20 (21) ◽  
pp. 5493 ◽  
Author(s):  
Meunier ◽  
Chea ◽  
Garrido ◽  
Perchet ◽  
Petit ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Nk Cell ◽  
Lymphoid Cells ◽  
Inflammatory Conditions ◽  
Airway Diseases ◽  
Type 2 Cytokines ◽  
Lymphoid Organogenesis ◽  
Deficient Mice

Innate lymphoid cells (ILC) are important players of early immune defenses in situations like lymphoid organogenesis or in case of immune response to inflammation, infection and cancer. Th1 and Th2 antagonism is crucial for the regulation of immune responses, however mechanisms are still unclear for ILC functions. ILC2 and NK cells were reported to be both involved in allergic airway diseases and were shown to be able to interplay in the regulation of the immune response. CXCR6 is a common chemokine receptor expressed by all ILC, and its deficiency affects ILC2 and ILC1/NK cell numbers and functions in lungs in both steady-state and inflammatory conditions. We determined that the absence of a specific ILC2 KLRG1+ST2– subset in CXCR6-deficient mice is probably dependent on CXCR6 for its recruitment to the lung under inflammation. We show that despite their decreased numbers, lung CXCR6-deficient ILC2 are even more activated cells producing large amount of type 2 cytokines that could drive eosinophilia. This is strongly associated to the decrease of the lung Th1 response in CXCR6-deficient mice.

scholarly journals Group 2 Innate Lymphoid Cells: A Double-Edged Sword in Cancer?

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3452
Author(s):  
Enrico Maggi ◽  
Irene Veneziani ◽  
Lorenzo Moretta ◽  
Lorenzo Cosmi ◽  
Francesco Annunziato
Keyword(s):  
Immune Response ◽  
Inflammatory Responses ◽  
Cell Subset ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Th2 Cell ◽  
Type 2 Immune Response ◽  
Group 2 ◽  
Lymphoid Organogenesis

Group 2 Innate Lymphoid Cells (ILC2s) belong to the family of helper ILCs which provide host defense against infectious agents, participate in inflammatory responses and mediate lymphoid organogenesis and tissue repair, mainly at the skin and mucosal level. Based on their transcriptional, phenotypic and functional profile, ILC2s mirror the features of the adaptive CD4+ Th2 cell subset, both contributing to the so-called type 2 immune response. Similar to other ILCs, ILC2s are rapidly activated by signals deriving from tissue and/or other tissue-resident immune cells. The biologic activity of ILCs needs to be tightly regulated in order to prevent them from contributing to severe inflammation and damage in several organs. Indeed, ILC2s display both enhancing and regulatory roles in several pathophysiological conditions, including tumors. In this review, we summarize the actual knowledge about ILC2s ability to induce or impair a protective immune response, their pro- or antitumor activity in murine models, human (children and adults) pathologies and the potential strategies to improve cancer immunotherapy by exploiting the features of ILC2s.

scholarly journals Dairy Heifers Naturally Exposed toFasciola hepaticaDevelop a Type 2 Immune Response and Concomitant Suppression of Leukocyte Proliferation

2017 ◽  
Vol 86 (1) ◽  
Author(s):  
John Graham-Brown ◽  
Catherine Hartley ◽  
Helen Clough ◽  
Aras Kadioglu ◽  
Matthew Baylis ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Peripheral Blood ◽  
Serum Antibody ◽  
Enzyme Linked Immunosorbent Assay ◽  
Mixed Effect ◽  
Content Type ◽  
Grazing Season ◽  
Type 2 Immune Response

ABSTRACTFasciola hepaticais a parasitic trematode of global importance in livestock. Control strategies reliant on anthelmintics are unsustainable due to the emergence of drug resistance. Vaccines are under development, but efficacies are variable. Evidence from experimental infection suggests that vaccine efficacy may be affected by parasite-induced immunomodulation. Little is known about the immune response toF. hepaticafollowing natural exposure. Hence, we analyzed the immune responses over time in calves naturally exposed toF. hepaticainfection. Cohorts of replacement dairy heifer calves (n= 42) with no prior exposure toF. hepatica, on three commercial dairy farms, were sampled over the course of a grazing season. Exposure was determined through anF. hepatica-specific serum antibody enzyme-linked immunosorbent assay (ELISA) and fluke egg counts. Concurrent changes in peripheral blood leukocyte subpopulations, lymphocyte proliferation, and cytokine responses were measured. Relationships between fluke infection and immune responses were analyzed by using multivariable linear mixed-effect models. All calves from one farm showed evidence of exposure, while cohorts from the remaining two farms remained negative over the grazing season. A type 2 immune response was associated with exposure, with increased interleukin-4 (IL-4) production, IL-5 transcription, and eosinophilia. Suppression of parasite-specific peripheral blood mononuclear cell (PBMC) proliferation was evident, while decreased mitogen-stimulated gamma interferon (IFN-γ) production suggested immunomodulation, which was not restricted to parasite-specific responses. Our findings show that the global immune response is modulated toward a nonproliferative type 2 state following natural challenge withF. hepatica. This has implications in terms of the timing of the administration of vaccination programs and for host susceptibility to coinfecting pathogens.

NKR-P1B Receptor Expression and Function in the Different Innate Lymphoid Cells of the Lung

2021 ◽  
Author(s):  
Lucas Vajko
Keyword(s):  
Nk Cell ◽  
Γδ T Cells ◽  
Bronchial Epithelium ◽  
Lung Parenchyma ◽  
Recognition System ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Receptor Expression ◽  
And Function ◽  
Deficient Mice

Group 2 innate lymphoid cells (ILC2) are the majority of ILCs in murine lungs at steady state. ILC2s are the main producer of type-2-cytokines, IL-4, IL-5, IL-9, IL-13, and amphiregulin, playing key roles in lung tissue homeostasis, airway responses to pathogens and allergens, and in cancer-related defenses. ILC functions are regulated by cell surface receptors. NKR-P1B is an inhibitory receptor, which recognizes C-type lectin-related protein (Clr-b) as its ligand. NKR-P1B is expressed on subsets of natural killer cells, ILC2, ILC3, γδ T cells, macrophages and dendritic cells in a tissue-specific manner and regulates NK cell and ILC3 functions in the gut. Expression and function of NKR-P1B in the lung ILC populations is unexplored. Moreover, Clr-b, the ligand for NKR-P1B, is expressed in the bronchial epithelium, endothelial cells and in lung parenchyma, but its role in immune regulation in the lung is unknown. We hypothesize that ILC2s in the lung express NKR-P1B, and their function is regulated by the NKR-P1B:Clr-b recognition system. Using wild-type (WT) and NKR-P1B-deficient mice, we study the expression of NKR-P1B on lung ILC2, and the function of NKR-P1B:Clr-b recognition system in ILC2 development and function. We compare the phenotype, frequency, numbers and cytokine production by ILC2s upon stimulation between WT and NKR-P1B-deficient mice using antibody staining and flow cytometry analysis. This study will reveal the role of NKR-P1B as a model system for its human homolog, NKR-P1A, in the regulation of ILC development and function, advancing our understanding of how immune responses in the lung are regulated.

scholarly journals NK cell recruitment limits tissue damage during an enteric helminth infection

2019 ◽  
Vol 13 (2) ◽  
pp. 357-370 ◽  
Author(s):  
Maria E. Gentile ◽  
Yue Li ◽  
Amicha Robertson ◽  
Kathleen Shah ◽  
Ghislaine Fontes ◽  
...  
Keyword(s):  
Immune Response ◽  
Nk Cells ◽  
Helminth Infection ◽  
Nk Cell ◽  
Early Response ◽  
Cell Recruitment ◽  
Parasitic Helminths ◽  
Cxcr3 Expression ◽  
Type 2 Immune Response

AbstractParasitic helminths cause significant damage as they migrate through host tissues to complete their life cycle. While chronic helminth infections are characterized by a well-described Type 2 immune response, the early, tissue-invasive stages are not well understood. Here we investigate the immune pathways activated during the early stages of Heligmosomoides polygyrus bakeri (Hpb), a natural parasitic roundworm of mice. In contrast to the Type 2 immune response present at later stages of infection, a robust Type 1 immune signature including IFNg production was dominant at the time of parasite invasion and granuloma formation. This early response was associated with an accumulation of activated Natural Killer (NK) cells, with no increase of other innate lymphoid cell populations. Parabiosis and confocal microscopy studies indicated that NK cells were recruited from circulation to the small intestine, where they surrounded parasitic larvae. NK cell recruitment required IFNγ receptor signaling, but was independent of CXCR3 expression. The depletion of tissue-infiltrating NK cells altered neither worm burden nor parasite fitness, but increased vascular injury, suggesting a role for NK cells in mediating tissue protection. Together, these data identify an unexpected role for NK cells in promoting disease tolerance during the invasive stage of an enteric helminth infection.

scholarly journals Dietary Selenium in Immune Mechanisms During an Enteric Bacterial Infection (OR12-08-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Shaneice Nettleford ◽  
Luming Zhao ◽  
James Fraser ◽  
Adwitia Dey ◽  
Dhimant Desai ◽  
...  
Keyword(s):  
Immune Responses ◽  
Trace Element ◽  
Lymphoid Cells ◽  
Nutritional Deficiencies ◽  
Enteric Infection ◽  
Bacterial Burden ◽  
Citrobacter Rodentium ◽  
T Helper 17 ◽  
Western Blots ◽  
Deficient Mice

Abstract Objectives Enteropathogenic Escherichia coli (EPEC) poses a great threat to developing countries, as EPEC can result in diarrhea and colitis in children. Interestingly, the effect of trace element nutritional deficiencies as well as their supplementation on disease pathogenesis is increasingly being recognized. We have previously reported that supplementation of mice with selenium (Se), a trace element that is incorporated into selenoproteins as the 21st amino acid, resulted in the amelioration of chemically induced colitis through the downregulation of pro-inflammatory mediators of the arachidonic acid pathway, including prostaglandin E2 (PGE2). Here we examined the effects of Se supplementation on immune responses during an enteric infection with Citrobacter rodentium, a natural murine enteropathogen. Methods C57BL/6 mice placed on Se-deficient (0.01 ppm Se), Se-adequate (0.08 ppm Se), or Se-supplemented (0.4 ppm Se) diets for 8 weeks were infected with Citrobacter rodentium, the murine equivalent of EPEC with a shared core set of virulence factors. Mice were euthanized, and colons were collected for further analysis including western blots and flow cytometry. Results Se-deficient mice experienced increased bacterial burden, mortality, and decreased colon length following infection, compared to Se-adequate and Se-supplemented mice. Studies revealed that there was an increase type 3 innate-lymphoid cells (ILC3s) and IL-22 producing T helper 17 (Th17) cells, but a decrease in regulatory T- cells (Tregs) and 15-prostaglandin dehydrogenase (15-PGDH), the enzyme that preferentially oxidizes PGE2, in the colon of Se-deficient mice compared to Se-adequate and Se-supplemented mice. Treatment of Se-adequate mice with CAY10397, an inhibitor of 15-PGDH, increased the bacterial burden following infection. Infection of mice that lack expression of selenoproteins in macrophages (Trspfl/fl LysMCre) showed increased mortality despite being fed diets replete with Se. Conclusions Adequate to supplemental levels of dietary Se is required to maximize the expression of selenoproteins to effectively mediate resolution of enteric infections. Selenoproteins act through diverse mechanisms, including modulation of immune responses and inflammation through the oxidative metabolism of PGE2. Funding Sources National Institute of Health.

scholarly journals 2019 ATVB Plenary Lecture

2020 ◽  
Vol 40 (4) ◽  
pp. 853-864 ◽  
Author(s):  
Tian X. Zhao ◽  
Stephen A. Newland ◽  
Ziad Mallat
Keyword(s):  
Cardiovascular Disease ◽  
T Cells ◽  
Regulatory T Cells ◽  
Immune Responses ◽  
Interleukin 2 ◽  
Cell Types ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Myocardial Repair

Regulatory T cells and type-2 innate lymphoid cells represent 2 subsets of immune cells, which have been shown in preclinical models to be important in atherosclerosis and myocardial repair. Regulatory T cells play a crucial role in immune homeostasis and tolerance via their interactions with effector T cells, dendritic cells, and monocytes/macrophages. They also utilize and secrete inhibitory cytokines, including interleukin 10 and transforming growth factor β, to regulate or suppress pathogenic immune responses. Type-2 innate lymphoid cells have an important role in type-2 immune responses and tissue repair through secreting interleukins 5 and 13, as well as a variety of biological mediators and growth factors. Intriguingly, interleukin-2 has emerged as a common cytokine, which can be harnessed to upregulate both cell types, and also has important translational consequences as clinical trials are ongoing for its use in cardiovascular disease. Here, we briefly review the biology of these regulatory immune cell types, discuss the preclinical and clinical evidence for their functions in cardiovascular disease, examine the prospects for clinical translation and current ongoing trials, and finally, postulate how overlap in the mechanisms of upregulation may be leveraged in future treatments for patients.

scholarly journals Bronchiolitis and recurrent wheezing are distinguished by type 2 innate lymphoid cells and immune response

2020 ◽  
Vol 32 (1) ◽  
pp. 51-59
Author(s):  
Beatriz Sastre ◽  
María Luz García‐García ◽  
José Antonio Cañas ◽  
Cristina Calvo ◽  
José Manuel Rodrigo‐Muñoz ◽  
...  
Keyword(s):  
Immune Response ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Recurrent Wheezing

scholarly journals Regulation and Function of the Interleukin 13 Receptor α 2 During a T Helper Cell Type 2–dominant Immune Response

2003 ◽  
Vol 197 (6) ◽  
pp. 687-701 ◽  
Author(s):  
Monica G. Chiaramonte ◽  
Margaret Mentink-Kane ◽  
Bruce A. Jacobson ◽  
Allen W. Cheever ◽  
Matthew J. Whitters ◽  
...  
Keyword(s):  
Immune Response ◽  
Airway Hyperreactivity ◽  
T Helper Cell ◽  
Helper Cell ◽  
T Helper ◽  
Fibrotic Response ◽  
Tissue Eosinophilia ◽  
Nematode Parasites ◽  
Deficient Mice

Highly polarized type 2 cytokine responses can be harmful and even lethal to the host if they are too vigorous or persist too long. Therefore, it is important to elucidate the mechanisms that down-regulate these reactions. Interleukin (IL)-13 has emerged as a central mediator of T helper cell (Th)2-dominant immune responses, exhibiting a diverse array of functional activities including regulation of airway hyperreactivity, resistance to nematode parasites, and tissue remodeling and fibrosis. Here, we show that IL-13 receptor (R)α2 is a critical down-regulatory factor of IL-13–mediated tissue fibrosis induced by the parasitic helminth Schistosoma mansoni. IL-13Rα2 expression was induced after the onset of the fibrotic response, IL-10, IL-13, and Stat6 dependent, and inhibited by the Th1-inducing adjuvant IL-12. Strikingly, schistosome-infected C57BL/6 and BALB/c IL-13Rα2–deficient mice showed a marked exacerbation in hepatic fibrosis, despite displaying no change in granuloma size, tissue eosinophilia, or mastocytosis. Fibrosis increased despite the fact that IL-13 levels decreased significantly in the liver and serum. Importantly, pathology was prevented when IL-13Rα2–deficient mice were treated with a soluble IL-13Rα2-Fc construct, formally demonstrating that their exacerbated fibrotic response was due to heightened IL-13 activity. Together, these studies illustrate the central role played by the IL-13Rα2 in the down-regulation of a chronic and pathogenic Th2-mediated immune response.

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