Stem cells, inflammation and allergy

Abstract

Recently, many studies have suggested a potential role for early hematopoietic progenitor cell and hematopoietic stem cell (HSC) recruitment and differentiation in the development of allergy and inflammation. This is based largely on evidence that stem cells or CD34+ progenitor cells are recruited to the site of inflammation in allergic diseases, likely through many of the same adhesion and chemokine receptors used for stem cell homing to the bone marrow (PSGL-1, CXCL12, alpha4-beta1 integrin, CD44, etc). Once at the site of inflammation, it has been suggested that stem cells could participate in the perpetuation of inflammation by maturing, locally, into inflammatory cells in response to the growth factors released in situ. Here we provide a brief review of the evidence to suggest that hematopoietic stem and progenitor cells (versus mature hematopoietic lineages) are, indeed, recruited to the site of allergic inflammation. We also discuss the molecules that likely play a role in this process, and highlight a number of our novel observations on a specific role for the stem cell antigen CD34 in this process.

Figure 1

Mouse and human expression of shared molecules between inflammation and stem cells. Comparison of mouse and human expression of 1) bone marrow homing molecules influencing inflammation, 2) inflammatory molecules influencing bone marrow trafficking and 3) inflammatory cytokines produced by hematopoietic stem cells.

Figure 2

Inflammatory receptors and mediators shared between stem cells and inflammatory cells. List of inflammatory receptors and mediators shared between stem cells and inflammatory cells. Modulation of these mediators/receptors was reported to mediate stem cell mobilising, which could allow them to contribute to development of inflammatory and allergic diseases. *: receptors that were reported to be expressed in stem cells.

Figure 3

Proposed models for the role of stem cells in development of inflammation. A) Production of inflammatory mediators during inflammation can increase the number of committed progenitor cells. B) Chemotactic mediators released during inflammation can provoke the recruitment of stem cells from the circulation to the site of inflammation where they undergo a rapid proliferation phase, followed by terminal differentiation into inflammatory cells (mast cells, dendritic cells, eosinophils, neutrophils, etc) at the site of the inflammatory reaction, contributing to development and chronicity of disease. C) Inflammatory mediators provoke the release of proteases (MMPs) by granulocytes or stem cells within the bone marrow, which cleave the molecular anchors of stem cells and increase their release in the circulation.