Toll‐like receptor‐induced expression of epithelial cytokine receptors on haemopoietic progenitors is altered in allergic asthma

Abstract

These data demonstrate an interaction between allergen and TLR ligand exposure in asthmatics. Allergen inhalation augments the TLR-induced inflammatory response by HPC, possibly leading to increased "in situ haemopoiesis" through up-regulation of TSLPR. These findings show that HPC may be a part of the pro-inflammatory cascade in pathogen-induced asthma exacerbation through their increased responsiveness to TLR stimulation.

Shaping eosinophil identity in the tissue contexts of development, homeostasis, and disease

“…CD34 eosinophil precursors also express functional TLR4 with the potential to influence hematopoietic decisions . Importantly, TLR4 stimulation of human HSCs yields higher numbers of TSLPR+ cells in asthmatics compared with healthy subjects . It is still unknown to what extent in situ hematopoiesis contributes to the generation of eosinophils at tissue sites as opposed to the recruitment of eosinophils from bone marrow and circulation.…”

Toll-like receptors-mediated pathways activate inflammatory responses in the esophageal mucosa of adult eosinophilic esophagitis

“…Some allergens (such as the major house dust mite allergen or Derp2) show a structural homology with MD2 protein, which is a co-mediator of TLR-4 activation 54 , 63 , and could activate TLR-4-mediated response by a molecular mimicry mechanism. In contrast to TLR-1 and 2, stimulation of TLR-4 increases the activation of FcεRI and promotes Th2-type cytokines involved in eosinophilic responses, as documented in respiratory tract allergy 64 . In resting conditions, TLR-4 expression is reduced in bronchial mucosal referred to TLR-2, with the TLR-2/4 ratio determining the final sense of the FcεRI activation 65 , 66 .…”

Cord blood hemopoietic cell receptor expression is associated with early life atopic risk and lung function

“…We previously reported associations between HPC frequency and their expression of innate immune receptors in neonates with atopic mothers and in adult asthmatics following allergen challenge. 1,2 Here, we report the results of our prospective investigation into whether the cord blood of neonates carries patterns of cell expression separating at-risk infants from healthy. We used 60 children participating in the Canadian Healthy Infant Longitudinal Development (CHILD) Study 3 and examined HPC and DC receptor expression at birth in relation to the development of atopy and allergic disease, and to lung function (as measured by lung clearance index (LCI)) at ages 1 and 3.…”

“…Longitudinal birth cohort studies and follow-up of wheezy infants suggest that airway hyperresponsiveness (AHR), a hallmark of asthma, is determined already in infancy. 1,2 It is not known whether such an early establishment of AHR is linked to early morphological alterations related to wheezing disorders. Airway remodeling is a characteristic feature of asthma, characterized by structural changes such as epithelial injury, thickening of reticular basement membrane (RBM), and increased airway smooth muscle (ASM) mass.…”