Clin Transl Allergy. 2015 Jul 6;5:23. doi: 10.1186/s13601-015-0068-5. eCollection 2015.
Innate lymphocyte cells in asthma phenotypes.
Ozyigit LP1, Morita H2, Akdis M2.
Author information
Abstract
T helper type 2 (TH2) cells were previously thought to be the main initiating effector cell type in asthma; however, exaggerated TH2 cell activities alone were insufficient to explain all aspects of asthma. Asthma is a heterogeneous syndrome comprising different phenotypes that are characterized by their different clinical features, treatment responses, and inflammation patterns. The most-studied subgroups of asthma include TH2-associated early-onset allergic asthma, late-onset persistent eosinophilic asthma, virus-induced asthma, obesity-related asthma, and neutrophilic asthma. The recent discovery of human innate lymphoid cells capable of rapidly producing large amounts of cytokines upon activation and the mouse data pointing to an essential role for these cells in asthma models have emphasized the important role of the innate immune system in asthma and have provided a new means of better understanding asthma mechanisms and differentiating its phenotypes.
KEYWORDS:
Airways; Asthma; Cytokines; Innate immunity; Phenotype
http://www.ncbi.nlm.nih.gov/pubmed/26150907
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4491887/
Mediators Inflamm. 2015;2015:879783. doi: 10.1155/2015/879783. Epub 2015 Mar 23.
Cellular mechanisms underlying eosinophilic and neutrophilic airway inflammation in asthma.
Pelaia G1, Vatrella A2, Busceti MT1, Gallelli L3, Calabrese C4, Terracciano R3, Maselli R1.
Author information
Abstract
Asthma is a phenotypically heterogeneous chronic disease of the airways, characterized by either predominant eosinophilic or neutrophilic, or even mixed eosinophilic/neutrophilic inflammatory patterns. Eosinophilic inflammation can be associated with the whole spectrum of asthma severity, ranging from mild-to-moderate to severe uncontrolled disease, whereas neutrophilic inflammation occurs mostly in more severe asthma. Eosinophilic asthma includes either allergic or nonallergic phenotypes underlying immune responses mediated by T helper (Th)2 cell-derived cytokines, whilst neutrophilic asthma is mostly dependent on Th17 cell-induced mechanisms. These immune-inflammatory profiles develop as a consequence of a functional impairment of T regulatory (Treg) lymphocytes, which promotes the activation of dendritic cells directing the differentiation of distinct Th cell subsets. The recent advances in the knowledge of the cellular and molecular mechanisms underlying asthmatic inflammation are contributing to the identification of novel therapeutic targets, potentially suitable for the implementation of future improvements in antiasthma pharmacologic treatments.
http://www.ncbi.nlm.nih.gov/pubmed/25878402
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4386709/
J Allergy Clin Immunol. 2012 Jan;129(1):216-27.e1-6. doi: 10.1016/j.jaci.2011.10.036. Epub 2011 Nov 25.
Innate lymphoid cells responding to IL-33 mediate airway hyperreactivity independently of adaptive immunity.
Kim HY1, Chang YJ, Subramanian S, Lee HH, Albacker LA, Matangkasombut P, Savage PB, McKenzie AN, Smith DE, Rottman JB, DeKruyff RH, Umetsu DT.
Author information
Abstract
BACKGROUND:
Asthma has been considered an immunologic disease mediated by T(H)2 cells and adaptive immunity. However, clinical and experimental observations suggest that additional pathways might regulate asthma, particularly in its nonallergic forms, such as asthma associated with air pollution, stress, obesity, and infection.
OBJECTIVES:
Our goal was to understand T(H)2 cell-independent conditions that might lead to airway hyperreactivity (AHR), a cardinal feature of asthma.
METHODS:
We examined a murine model of experimental asthma in which AHR was induced with glycolipid antigens, which activate natural killer T (NKT) cells.
RESULTS:
In this model AHR developed rapidly when mice were treated with NKT cell-activating glycolipid antigens, even in the absence of conventional CD4(+) T cells. The activated NKT cells directly induced alveolar macrophages to produce IL-33, which in turn activated NKT cells, as well as natural helper cells, a newly described non-T, non-B, innate lymphoid cell type, to increase production of IL-13. Surprisingly, this glycolipid-induced AHR pathway required not only IL-13 but also IL-33 and its receptor, ST2, because it was blocked by an anti-ST2 mAb and was greatly reduced in ST2(-/-) mice. When adoptively transferred into IL-13(-/-) mice, both wild-type natural helper cells and NKT cells were sufficient for the development of glycolipid-induced AHR.
CONCLUSION:
Because plant pollens, house dust, and some bacteria contain glycolipids that can directly activate NKT cells, these studies suggest that AHR and asthma can fully develop or be greatly enhanced through innate immune mechanisms involving IL-33, natural helper cells, and NKT cells.
Copyright © 2011 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.
http://www.ncbi.nlm.nih.gov/pubmed/22119406
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3246069/
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4490858/
Innate lymphocyte cells in asthma phenotypes.
Ozyigit LP1, Morita H2, Akdis M2.
Author information
Abstract
T helper type 2 (TH2) cells were previously thought to be the main initiating effector cell type in asthma; however, exaggerated TH2 cell activities alone were insufficient to explain all aspects of asthma. Asthma is a heterogeneous syndrome comprising different phenotypes that are characterized by their different clinical features, treatment responses, and inflammation patterns. The most-studied subgroups of asthma include TH2-associated early-onset allergic asthma, late-onset persistent eosinophilic asthma, virus-induced asthma, obesity-related asthma, and neutrophilic asthma. The recent discovery of human innate lymphoid cells capable of rapidly producing large amounts of cytokines upon activation and the mouse data pointing to an essential role for these cells in asthma models have emphasized the important role of the innate immune system in asthma and have provided a new means of better understanding asthma mechanisms and differentiating its phenotypes.
KEYWORDS:
Airways; Asthma; Cytokines; Innate immunity; Phenotype
http://www.ncbi.nlm.nih.gov/pubmed/26150907
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4491887/
Mediators Inflamm. 2015;2015:879783. doi: 10.1155/2015/879783. Epub 2015 Mar 23.
Cellular mechanisms underlying eosinophilic and neutrophilic airway inflammation in asthma.
Pelaia G1, Vatrella A2, Busceti MT1, Gallelli L3, Calabrese C4, Terracciano R3, Maselli R1.
Author information
Abstract
Asthma is a phenotypically heterogeneous chronic disease of the airways, characterized by either predominant eosinophilic or neutrophilic, or even mixed eosinophilic/neutrophilic inflammatory patterns. Eosinophilic inflammation can be associated with the whole spectrum of asthma severity, ranging from mild-to-moderate to severe uncontrolled disease, whereas neutrophilic inflammation occurs mostly in more severe asthma. Eosinophilic asthma includes either allergic or nonallergic phenotypes underlying immune responses mediated by T helper (Th)2 cell-derived cytokines, whilst neutrophilic asthma is mostly dependent on Th17 cell-induced mechanisms. These immune-inflammatory profiles develop as a consequence of a functional impairment of T regulatory (Treg) lymphocytes, which promotes the activation of dendritic cells directing the differentiation of distinct Th cell subsets. The recent advances in the knowledge of the cellular and molecular mechanisms underlying asthmatic inflammation are contributing to the identification of novel therapeutic targets, potentially suitable for the implementation of future improvements in antiasthma pharmacologic treatments.
http://www.ncbi.nlm.nih.gov/pubmed/25878402
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4386709/
J Allergy Clin Immunol. 2012 Jan;129(1):216-27.e1-6. doi: 10.1016/j.jaci.2011.10.036. Epub 2011 Nov 25.
Innate lymphoid cells responding to IL-33 mediate airway hyperreactivity independently of adaptive immunity.
Kim HY1, Chang YJ, Subramanian S, Lee HH, Albacker LA, Matangkasombut P, Savage PB, McKenzie AN, Smith DE, Rottman JB, DeKruyff RH, Umetsu DT.
Author information
Abstract
BACKGROUND:
Asthma has been considered an immunologic disease mediated by T(H)2 cells and adaptive immunity. However, clinical and experimental observations suggest that additional pathways might regulate asthma, particularly in its nonallergic forms, such as asthma associated with air pollution, stress, obesity, and infection.
OBJECTIVES:
Our goal was to understand T(H)2 cell-independent conditions that might lead to airway hyperreactivity (AHR), a cardinal feature of asthma.
METHODS:
We examined a murine model of experimental asthma in which AHR was induced with glycolipid antigens, which activate natural killer T (NKT) cells.
RESULTS:
In this model AHR developed rapidly when mice were treated with NKT cell-activating glycolipid antigens, even in the absence of conventional CD4(+) T cells. The activated NKT cells directly induced alveolar macrophages to produce IL-33, which in turn activated NKT cells, as well as natural helper cells, a newly described non-T, non-B, innate lymphoid cell type, to increase production of IL-13. Surprisingly, this glycolipid-induced AHR pathway required not only IL-13 but also IL-33 and its receptor, ST2, because it was blocked by an anti-ST2 mAb and was greatly reduced in ST2(-/-) mice. When adoptively transferred into IL-13(-/-) mice, both wild-type natural helper cells and NKT cells were sufficient for the development of glycolipid-induced AHR.
CONCLUSION:
Because plant pollens, house dust, and some bacteria contain glycolipids that can directly activate NKT cells, these studies suggest that AHR and asthma can fully develop or be greatly enhanced through innate immune mechanisms involving IL-33, natural helper cells, and NKT cells.
Copyright © 2011 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.
http://www.ncbi.nlm.nih.gov/pubmed/22119406
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3246069/
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4490858/