Allergen-induced Changes in Bone Marrow and Airway Dendritic Cells in Subjects with Asthma

Abstract

Inhaled allergen increases DCs in bone marrow and trafficking of DCs into the airway, which is associated with the development airway inflammation in subjects with allergic asthma. Inhaled allergen challenge also increases expression of TSLP, but not IL-33, receptors on bone marrow DCs.

Tissue‐resident innate immunity in the lung

“…119 The pDCs may also play a tolerogenic role in allergic lung inflammation, at least in part through up-regulation of the Tcell inhibitory ligand PD-L1. [122][123][124][125] Interestingly, asthma in humans has been linked to a lack of exposure to environmental bacteria such as Helicobacter pylori, and sensitization of mice with H. pylori extract prevents subsequent allergic inflammation. 121 In humans, both cDC1s and cDC2s are reported to be expanded in the lungs of individuals with asthma following allergen challenge, and promote Th2 and Th9 responses, although this is not always consistent.…”

Worms: Pernicious parasites or allies against allergies?

“…Interestingly, cDC1 can also have a tolerogenic function in allergy models: they induce Treg cells via retinoic acid and peroxisome proliferator‐activated receptor gamma (PPARγ) and limit inflammation in a HDM and ovalbumin model of allergic airway inflammation and during schistosome infections . In patients with asthma, increased numbers of DCs are found in the blood, induced sputum and bronchoalveolar lavage upon allergen challenge, but only cDC2 migrated into the bronchial tissue . The DCs express more OX‐40L, a molecule involved in Th2 polarization and more FcεRI .…”

“…146 In patients with asthma, increased numbers of DCs are found in the blood, induced sputum and bronchoalveolar lavage upon allergen challenge, but only cDC2 migrated into the bronchial tissue. 147 The DCs express more OX-40L, a molecule involved in Th2 polarization 148 and more FcεRI. 149 In the absence of DCs, type 2 responses in allergy models are profoundly abrogated, 150 but other myeloid cell populations may also be important to support Th2 cell development in either allergy models or helminth infection, like monocyte-derived dendritic cells.…”

Dendritic Cells in Human Lung Disease

“…In people with allergic asthma, allergen inhalation has proved an effective method for studying the dynamics of DC migration, as it induces increased numbers of sputum cDC, including both CD11c+ and CD141+ subsets 14,18 . Allergen challenge also increases numbers of bone marrow cDC, upregulating TSLP receptor but not IL-33 receptor on bone marrow DC, and primes bone marrow progenitors to differentiate into DC in response to haemopoietic growth factors 19 . Studies in experimental asthma models have shown that airway derived prostaglandins can exert long lived immunomodulatory effects on DC progenitors in bone marrow 20 , though whether this also occurs in persistent human asthma has yet to be determined.…”

“…With respect to pDC, a number of reports indicate that lung pDC are recruited to the airway lumen following allergen inhalation 14,29 , and this is associated with elevated numbers of bone marrow pDC 19 . There is no consensus in the literature on whether circulating pDC numbers differ between adults with asthma and healthy individuals 30,31 , though it is likely that pDC fluctuate over time in responses to environmental exposures, especially virus infections.…”