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Hematopoietic stem/progenitor cells in inflammation and allergy

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Hematopoietic stem/progenitor cells (HSPCs) reside within the bone marrow (BM) where they give rise to all hematopoietic populations. In steady state conditions, hematopoietic progenitors constantly egress from the BM into the blood, and circulate through the peripheral tissues where upon encounter with ...

Hematopoietic stem/progenitor cells (HSPCs) reside within the bone marrow (BM) where they give rise to all hematopoietic populations. In steady state conditions, hematopoietic progenitors constantly egress from the BM into the blood, and circulate through the peripheral tissues where upon encounter with inflammatory stimuli they may differentiate into tissue dwelling and effector cells. In the allergic diseases, the number of BM and circulating progenitor cells increases during exacerbation of asthma or after allergen challenge and they accumulate in the bronchial mucosa and the sputum of allergic asthmatics. Circulating CD34+ progenitor cells migrating to the site of allergic inflammation differentiate into mast cells, eosinophils and basophils, the typical effector cells of allergic responses, and may also contribute directly or indirectly to the differentiation of tissue dwelling cells involved in the remodelling of the airway structure, such as endothelial cells and myofibroblasts. However, recent data indicated that shortly after their recruitment to the site of inflammation/injury, HSPCs rapidly release very high levels of Th2 cytokines/chemokines in response to thymic stromal lymphopoietin (TSLP) and IL-33, even before their differentiation into effector cells. This novel concept of their dual function as precursors and potent Th2 cytokine producers has important clinical implications in various inflammatory conditions including allergic diseases. Th2 profile of molecules released by the activated progenitors will also permit to appreciate their protective involvement in cardiovascular diseases, ischemia, and wound healing. We still do not fully appreciate the role of progenitor cells in these healing/inflammatory processes. Understanding these early innate Th2 type immune responses and inflammatory mediators that are important for the initiation of these responses will be the key to designing novel therapies.

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