Mechanisms of allergy and clinical immunology: CD34 hemopoietic progenitor cells are potent effectors of allergic inflammation

Background: In steady state, hemopoietic progenitors constantly egress from the bone marrow (BM) into the blood and circulate through the peripheral tissues. In allergic diseases, the BM releases increased numbers of CD34+ progenitor cells that migrate to the site of allergic inflammation, where they differentiate into tissue-dwelling and classic effector cells of allergy, such as mast cells, eosinophils, and basophils. Objective To examine whether peripheral blood CD34+ cells in addition to being progenitors may also directly function as inflammatory effector cells. Methods Highly purified neonatal or adult blood CD34+ cells were examined for the expression of thymic stromal lymphopoietin (TSLP) and IL-33 receptors and for their response to these cytokines as well as to supernatants of primary small airway epithelial cells and nasal explants from rhinosinusitis and control subjects. Sputum of patients with asthma was examined before and after allergen inhalation for the presence of IL-5 and IL-13-containing CD34+ cells. Results Circulating CD34+ cells expressed receptors for TSLP and IL-33 and responded to these cytokines by rapidly releasing high levels of proinflammatory TH2-like cytokines and chemokines. These cells were activated in a TSLP-dependent manner by the supernatant fluids from activated primary human small airway epithelial cells and from nasal explants of patients with chronic rhinosinusitis. Moreover, activated CD34+ cells containing IL-5 and IL-13 could be detected in the sputum of individuals with allergic asthma, with numbers increasing in response to specific allergen inhalation challenge. Conclusion Blood CD34+ cells, in addition to being progenitors, may act as proinflammatory effector cells by themselves and directly contribute to the allergic inflammation.