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Targeting Group 2 Innate Lymphoid Cells (ILC2) in Disease: Central Regulators in Immunity, Tissue Homeostasis, and Physiology

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (30 June 2019) | Viewed by 32195

Special Issue Editor

Department of Microbiology and Immunology, McGill University Research Center on Complex Traits, FOCiS Centre of Excellence in Translational Immunology (CETI), McGill University, Montréal, QC, Canada
Interests: mucosal immunology; chronic disease; infectious disease biology; vaccinology; immunotherapy; type 2 immunopathologies; innate immunity

Special Issue Information

Dear Colleagues,

Group 2 innate lymphoid cells (ILC2), members of the family of innate lymphoid cells (ILC), are tissue-resident sentinels that respond rapidly to their environment through soluble inflammatory mediators, neurotrophic factors and cell-to-cell interactions. ILC2s participate in shaping appropriate immune responses during infection and inflammation and contribute to preserving the delicate equilibrium of tissue homeostasis after immune challenge. ILC2 help orchestrate innate and adaptive type 2 immunity in diverse immune processes, distinct anatomical sites and tissues. They participate to establish protective immunity, but when deregulated contribute to pathological disorders including asthma, allergy and atopic dermatitis. In addition, ILC2 have been shown to regulate inflammatory and metabolic processes and contribute to disease onset and outcome during obesity, type 2 diabetes and cancer. Therefore, ILC2 constitute an important nexus of the immune system and represent an attractive target for immune modulation in disease.

This Special Issue will focus on the integration of the role of ILC2 in biological processes and molecular and cellular events as they relate to the regulation of the immune system, tissue homeostasis, and physiology during health and disease.

We are seeking novel research and/or review articles highlighting

  • ILC2 development,
  • Molecular regulation of ILC2 and its impact on immunity and disease,
  • ILC2 diversity and functional polarization on immune challenge and during disease,
  • Redundancy between ILC2s and Th2 cells,
  • Cellular interaction of ILC2 (hematopoietic and non-hematopoietic cell lineages),
  • ILC2 function in health and disease,
  • ILC2 as drug targets;

Dr. Jörg Hermann Fritz
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Mucosal immunology
  • Infectious disease
  • Type 2 immunity
  • Inflammation
  • Cytokines
  • Cell–cell contact
  • Chronic inflammatory barrier disorders
  • Asthma and asthma exacerbations
  • Allergies
  • Atopic dermatitis
  • Fibrosis
  • Cancer
  • Type 2 diabetes
  • Fat homeostasis and obesity
  • Neuroinflammation
  • Neurotrophic factors
  • Tissue homeostasis and regeneration

Published Papers (6 papers)

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Research

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17 pages, 5032 KiB  
Article
Maintenance of Type 2 Response by CXCR6-Deficient ILC2 in Papain-Induced Lung Inflammation
by Sylvain Meunier, Sylvestre Chea, Damien Garrido, Thibaut Perchet, Maxime Petit, Ana Cumano and Rachel Golub
Int. J. Mol. Sci. 2019, 20(21), 5493; https://doi.org/10.3390/ijms20215493 - 04 Nov 2019
Cited by 8 | Viewed by 3569
Abstract
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 [...] Read more.
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. Full article
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Review

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18 pages, 1842 KiB  
Review
Group 2 Innate Lymphoid Cells: Central Players in a Recurring Theme of Repair and Regeneration
by Melina Messing, Sia Cecilia Jan-Abu and Kelly McNagny
Int. J. Mol. Sci. 2020, 21(4), 1350; https://doi.org/10.3390/ijms21041350 - 17 Feb 2020
Cited by 22 | Viewed by 5552
Abstract
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 [...] Read more.
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. Full article
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24 pages, 1376 KiB  
Review
ILC2 Activation by Protozoan Commensal Microbes
by Kyle Burrows, Louis Ngai, Flora Wong, David Won and Arthur Mortha
Int. J. Mol. Sci. 2019, 20(19), 4865; https://doi.org/10.3390/ijms20194865 - 30 Sep 2019
Cited by 10 | Viewed by 5742
Abstract
Group 2 innate lymphoid cells (ILC2s) are a member of the ILC family and are involved in protective and pathogenic type 2 responses. Recent research has highlighted their involvement in modulating tissue and immune homeostasis during health and disease and has uncovered critical [...] Read more.
Group 2 innate lymphoid cells (ILC2s) are a member of the ILC family and are involved in protective and pathogenic type 2 responses. Recent research has highlighted their involvement in modulating tissue and immune homeostasis during health and disease and has uncovered critical signaling circuits. While interactions of ILC2s with the bacterial microbiome are rather sparse, other microbial members of our microbiome, including helminths and protozoans, reveal new and exciting mechanisms of tissue regulation by ILC2s. Here we summarize the current field on ILC2 activation by the tissue and immune environment and highlight particularly new intriguing pathways of ILC2 regulation by protozoan commensals in the intestinal tract. Full article
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13 pages, 692 KiB  
Review
Group 2 Innate Lymphoid Cells (ILC2): Type 2 Immunity and Helminth Immunity
by De’Broski R. Herbert, Bonnie Douglas and Kelly Zullo
Int. J. Mol. Sci. 2019, 20(9), 2276; https://doi.org/10.3390/ijms20092276 - 08 May 2019
Cited by 72 | Viewed by 7665
Abstract
Group 2 innate lymphoid cells (ILC2) have emerged as a major component of type 2 inflammation in mice and humans. ILC2 secrete large amounts of interleukins 5 and 13, which are largely responsible for host protective immunity against helminth parasites because these cytokines [...] Read more.
Group 2 innate lymphoid cells (ILC2) have emerged as a major component of type 2 inflammation in mice and humans. ILC2 secrete large amounts of interleukins 5 and 13, which are largely responsible for host protective immunity against helminth parasites because these cytokines induce profound changes in host physiology that include: goblet cell metaplasia, mucus accumulation, smooth muscle hypercontractility, eosinophil and mast cell recruitment, and alternative macrophage activation (M2). This review covers the initial recognition of ILC2 as a distinct cell lineage, the key studies that established their biological importance, particularly in helminth infection, and the new directions that are likely to be the focus of emerging work that further explores this unique cell population in the context of health and disease. Full article
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20 pages, 1958 KiB  
Review
Type 2 Innate Lymphoid Cells in Liver and Gut: From Current Knowledge to Future Perspectives
by Aaron Ochel, Gisa Tiegs and Katrin Neumann
Int. J. Mol. Sci. 2019, 20(8), 1896; https://doi.org/10.3390/ijms20081896 - 17 Apr 2019
Cited by 11 | Viewed by 4595
Abstract
Innate lymphoid cells (ILCs) represent a heterogeneous population of recently discovered immune cells that mirror the functions of adaptive T lymphocytes. However, ILCs are devoid of specific antigen receptors and cellular activation depends on environmental cytokines, rendering them as early regulators of immune [...] Read more.
Innate lymphoid cells (ILCs) represent a heterogeneous population of recently discovered immune cells that mirror the functions of adaptive T lymphocytes. However, ILCs are devoid of specific antigen receptors and cellular activation depends on environmental cytokines, rendering them as early regulators of immune responses. Type 2 innate lymphoid cells (ILC2s) respond to alarmins, such as interleukin-25 and -33 and shape Th2-associated immunity by expressing IL-5 and IL-13 in a GATA3-dependent manner. In addition, ILC2s express the epidermal growth factor-like molecule Amphiregulin thereby promoting regeneration of injured tissue during inflammation. The gut and liver confer nutrient metabolism and bidirectional exchange of products, known as the gut-liver axis. Accordingly, both organs are continuously exposed to a large variety of harmless antigens. This requires avoidance of immunity, which is established by a tolerogenic environment in the gut and liver. However, dysregulations within the one organ are assumed to influence vitality of the other and frequently promote chronic inflammatory settings with poor prognosis. Intensive research within the last years has revealed that ILC2s are involved in acute and chronic inflammatory settings of gut and liver. Here, we highlight the roles of ILC2s in intestinal and hepatic inflammation and discuss a regulatory potential. Full article
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14 pages, 1561 KiB  
Review
Transcription Factors in the Development and Function of Group 2 Innate Lymphoid Cells
by Takashi Ebihara and Ichiro Taniuchi
Int. J. Mol. Sci. 2019, 20(6), 1377; https://doi.org/10.3390/ijms20061377 - 19 Mar 2019
Cited by 18 | Viewed by 4088
Abstract
Group 2 innate lymphoid cells (ILC2s) are tissue-resident cells and are a major source of innate TH2 cytokine secretion upon allergen exposure or parasitic-worm infection. Accumulating studies have revealed that transcription factors, including GATA-3, Bcl11b, Gfi1, RORα, and Ets-1, play a [...] Read more.
Group 2 innate lymphoid cells (ILC2s) are tissue-resident cells and are a major source of innate TH2 cytokine secretion upon allergen exposure or parasitic-worm infection. Accumulating studies have revealed that transcription factors, including GATA-3, Bcl11b, Gfi1, RORα, and Ets-1, play a role in ILC2 differentiation. Recent reports have further revealed that the characteristics and functions of ILC2 are influenced by the physiological state of the tissues. Specifically, the type of inflammation strongly affects the ILC2 phenotype in tissues. Inhibitory ILC2s, memory-like ILC2s, and ex-ILC2s with ILC1 features acquire their characteristic properties following exposure to their specific inflammatory environment. We have recently reported a new ILC2 population, designated as exhausted-like ILC2s, which emerges after a severe allergic inflammation. Exhausted-like ILC2s are featured with low reactivity and high expression of inhibitory receptors. Therefore, for a more comprehensive understanding of ILC2 function and differentiation, we review the recent knowledge of transcriptional regulation of ILC2 differentiation and discuss the roles of the Runx transcription factor in controlling the emergence of exhausted-like ILC2s. The concept of exhausted-like ILC2s sheds a light on a new aspect of ILC2 biology in allergic diseases. Full article
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