Abstract
Background: Shortly after allergen exposure, the number of bone marrow (BM) and circulating CD34+ progenitors increases. We aim to analyze the possible mechanism whereby the allergic reaction stimulates BM to release these effector cells in increased numbers. We hypothesize that mast cells (MCs) may play a predominant role in this process.Objective: To examine the effect of IgE-activated MCs on BM mesenchymal stromal cells which regulate proliferation and differentiation of CD34+ progenitors.Methods: Primary MCs were derived from CD34+ precursors and activated with IgE/anti-IgE. BM mesenchymal stromal cells were co-cultured with CD34+ progenitor cells and stimulated with IL-1/TNF or IgE/anti-IgE-activated MCs in Transwell system.Results: BM mesenchymal stromal cells produce low level of thymic stromal lymphopoietin (TSLP) under steady state conditions, which is markedly increased by stimulation with proinflammatory cytokines IL-1 and TNF or IgE-activated MCs. The latter also triggers bone marrow-derived mesenchymal stromal cells production of G-CSF, and GM-CSF while inhibiting SDF-1. MC-activated mesenchymal stromal cells stimulate CD34+ cells to proliferate and to regulate their expression of early allergy-associated genes.Conclusion and Clinical Relevance: This in vitro study indicates that IgE-activated MCs trigger BM mesenchymal stromal cells to release TSLP and hematopoietic growth factors and to regulate the proliferation and lineage commitment of CD34+ precursor cells. The data predict that the effective inhibition of MCs should impair mobilization and accumulation of allergic effector cells and thereby reduce the severity of allergic diseases.
Highlights
The initial manifestations of a mucosal allergic reaction are localized, recent studies underline a systemic component of allergic diseases and suggest an important role of the bone marrow (BM) in the control of allergic response
BM mesenchymal stromal cells produce low level of thymic stromal lymphopoietin (TSLP) under steady state conditions, which is markedly increased by stimulation with proinflammatory cytokines IL-1 and TNF or IgE-activated mast cells (MCs)
Relevance: This in vitro study indicates that IgE-activated MCs trigger BM mesenchymal stromal cells to release TSLP and hematopoietic growth factors and to regulate the proliferation and lineage commitment of CD34+ precursor cells
Summary
The initial manifestations of a mucosal allergic reaction are localized, recent studies underline a systemic component of allergic diseases and suggest an important role of the bone marrow (BM) in the control of allergic response. Shortly after allergen exposure BM releases increased numbers of CD34+ hematopoietic precursors and differentiated proinflammatory myeloid cells [1,2,3]. The specific mechanisms underlying airway allergen exposure and communication with the BM leading to augmented numbers of progenitor cells and their increased release remain to be elucidated. MCs originate from HSCs, which circulate as CD34+ precursors until they migrate into tissues where they mature to effector cells. Both CD34+ precursors and MCs actively participate in the induction of allergic inflammation by producing high levels of www.frontiersin.org. The number of bone marrow (BM) and circulating CD34+ progenitors increases. We hypothesize that mast cells (MCs) may play a predominant role in this process
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