Chapter 42 : Myeloid Cells in Asthma

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Asthma is clinically defined by variable airway obstruction that causes recurrent periods of shortness of breath, chest tightness, wheezing, and coughing. Patients also often have altered mucus production and have problems in expectorating sputa because of reduced viscosity of the mucus. One of the characteristic changes to lung physiology is the occurrence of bronchial hyperreactivity, which is defined as a tendency of the smooth muscle layer to contract to nonspecific stimuli like cold air or exercise, and measured in the lung function lab as increased bronchoconstriction to very low amounts of histamine or methacholine. We now realize that asthma is not one single disorder, but rather a syndrome or a spectrum of disease, characterized by endotypes that rely on distinct pathomechanisms and controlled by various adaptive or innate immune cells ( ). In early life, asthma is often allergic, driven by CD4 Th2 lymphocytes and associated with allergic comorbidity like atopic dermatitis and rhinitis. On histology, target organs often contain many eosinophils. In adult-onset asthma, almost half of the cases are not associated with allergy. Some of these patients have eosinophilic airway inflammation, whereas others have a neutrophil-predominant inflammation, a mixed neutrophil-eosinophil infiltration, or even pauci-immune disease. Important comorbidities are obesity, acid-reflux disease, and chronic rhinosinusitis ( ). Across all age groups, the presence of a more neutrophilic infiltrate is associated with more (therapy-resistant) severe disease, and it is possible that this disease variant relies more on interleukin-17 (IL-17)-producing Th17 cells ( ).

Citation: Lambrecht B, Persson E, Hammad H. 2017. Myeloid Cells in Asthma, p 739-757. In Gordon S (ed), Myeloid Cells in Health and Disease. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MCHD-0053-2016
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Figure 1

The early and late allergic response. This figure depicts the alterations in the airways, as well as the lung function alterations (measured as the amount of air being exhaled in 1 s in a forced expiratory maneuver, or FEV) in allergic patients before, during, and after an experimental allergen challenge. Before the challenge, the airways of asthmatics are hyperreactive (this does not always lead to reduced FEV). Minutes after allergen challenge, there is bronchoconstriction, and this is reflected by a drop in FEV that can sometimes be as much as 50% in very severe asthma attacks. This is called the early or immediate allergic response. After some 3 to 6 h, there is a second drop in FEV, this time accompanied by edema of the airway wall, cellular influx with inflammatory cells, and bronchoconstriction. This phase is called the late or delayed allergic response.

Citation: Lambrecht B, Persson E, Hammad H. 2017. Myeloid Cells in Asthma, p 739-757. In Gordon S (ed), Myeloid Cells in Health and Disease. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MCHD-0053-2016
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Image of Figure 2
Figure 2

The cellular interplay of myeloid and lymphoid cells in allergic asthma. (Left) A first allergen exposure leads to activation of CD11b cDC2s. This activation is direct or indirect, because lung epithelial cells make cytokines like IL-1, IL-33, IL-25, TSLP, and GM-CSF that mature the DCs. The same cytokines also activate basophils and ILC2, which control immediate innate eosinophilia. After a few hours, DCs will also arrive in the draining mediastinal nodes, where they will polarize adaptive immune cells to become Th2, Th21, and Th17 cells. B cells will be induced to secrete IgE. (Right) A recall response to allergens, which occurs continuously in patients allergic to perennial allergens. Upon repeated encounter with allergens, tissue mast cells and basophils are armed with IgE and release immediate mediators into the lung tissue, causing bronchoconstriction and local edema. Monocyte-derived cells (DCs and activated macrophages) will also take up allergens via IgE and this time present these allergens locally to T effector cells and resident memory Th2 cells. These effector cells reach the lungs because of chemokine production by monocyte-derived cells. The effector lymphocytes will also produce loss of IL-5, which boosts the production of eosinophils. These eosinophils migrate into the lungs and cause damage to the lung epithelium. In some cases, particularly when there is a Th17 response, neutrophils also will accumulate in the lungs. PGD, prostaglandin D. Modified from reference , with permission.

Citation: Lambrecht B, Persson E, Hammad H. 2017. Myeloid Cells in Asthma, p 739-757. In Gordon S (ed), Myeloid Cells in Health and Disease. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MCHD-0053-2016
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