Innate Cells and T Helper 2 Cell Immunity in Airway Inflammation

Department of Medicine, Harvard Medical School, and Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Boston, MA 02115, USA.
Immunity (Impact Factor: 21.56). 09/2009; 31(3):425-37. DOI: 10.1016/j.immuni.2009.08.014
Source: PubMed


Activated mast cells, eosinophils, and basophils infiltrate the airways of asthmatics as a result of an overexuberant T helper 2 (Th2) cell immune response that drives the production of IgE, primes mast cells and basophils, and promotes tissue eosinophilia and mast cell hyperplasia. Recent evidence demonstrates that these innate effectors can be activated outside of this classical Th2 cell paradigm and that they have additional roles in promoting the development of innate and adaptive pulmonary inflammation. There is also an appreciation for the role of airway epithelial cells in orchestrating allergic pulmonary inflammation. Emerging data from basic research highlight the involvement of many unique pathways in the inflammation triggered by complex native allergens and microbes at the airway mucosal surface. Here, we review the role of effector cells and airway epithelial cells in augmenting and, at times, bypassing traditional Th2 cell-mediated allergic inflammation.

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Available from: K. Frank Austen, Sep 23, 2014
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    • "During allergic sensitization, inhaled allergens are taken up by antigen-presenting dendritic cells in the airway and presented to T-cells.18 The cytokine milieu leads to T-helper cell differentiation and production of IL-4, IL-5, and IL-13, resulting in immunoglobulin (Ig)E class switching, eosinophil recruitment, mucus production, airway hyperresponsiveness, and remodeling features.19,20 IL-5 is a critical cytokine for eosinophil generation in the bone marrow, as well as eosinophil recruitment, activation, and survival. "
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    Journal of Asthma and Allergy 04/2014; 7(7):53-65. DOI:10.2147/JAA.S39119
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    • "Mast cells are effector cells that display various functions during immune response and regulate allergic inflammation, such as, those associated with asthma, atopic dermatitis, and sinusitis. Activated mast cells release pro-inflammatory cytokines, such as, tumour necrosis factor (TNF)-α, interleukin (IL)-6, IL-8, IL-13, and inflammatory mediators, including histamine, leukotrienes, serotonin, prostaglandin (PG)E2, and PGD2 (Barrett and Austen, 2009; Mukherjee and Zhang, 2011). The expressions of proinflammatory cytokines depend on the activations of the transcription factor, nuclear factor- κB (NF-κB), and mitogen-activated protein kinases (MAPKs), such as, extracellular signal-regulated kinase (ERK), p38, stress-activated protein kinases (SAPK)/c-Jun-N-terminal kinase (JNK) (Jeong et al., 2003; Rasheed et al., 2009). "
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    • "The other possible mechanism by which eosinophils contribute to the airway disease of asthma may be by adhesion to and then migrating across vascular endothelial cells. These processes are largely regulated by cytokines/chemokines produced by a variety of cells, including T-helper 2 (Th2) cells (Barrett and Austen, 2009 ▶). Not only eosinophilic inflammation but also neutrophilic inflammation may play roles in severe asthma, so that infiltration of these two cell types is increased into the airways of asthmatic patients. "
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