In situ hematopoiesis: a regulator of TH2 cytokine-mediated immunity and inflammation at mucosal surfaces

Abstract

Hematopoiesis refers to the development of blood cells in the body through the differentiation of pluripotent stem cells. Although hematopoiesis is a multifocal process during embryonic development, under homeostatic conditions it occurs exclusively within the bone marrow. There, a limited number of hematopoietic stem cells differentiate into a rapidly proliferating population of lineage-restricted progenitors that serve to replenish circulating blood cells. However, emerging reports now suggest that under inflammatory conditions, alterations in hematopoiesis that occur outside of the bone marrow appear to constitute a conserved mechanism of innate immunity. Moreover, recent reports have identified previously unappreciated pathways that regulate the egress of hematopoietic progenitor cells from the bone marrow, alter their activation status, and skew their developmental potential. These studies suggest that progenitor cells contribute to inflammatory response by undergoing in situ hematopoiesis (ISH). In this review, we highlight the differences between homeostatic hematopoiesis, which occurs in the bone marrow, and ISH, which occurs at mucosal surfaces. Further, we highlight factors produced at local sites of inflammation that regulate hematopoietic progenitor cell responses and the development of TH2 cytokine-mediated inflammation. Finally, we discuss the therapeutic potential of targeting ISH in preventing the development of inflammation at mucosal sites.

Increased numbers of activated group 2 innate lymphoid cells in the airways of patients with severe asthma and persistent airway eosinophilia

“…46,47 It has been shown that numbers of IL-5-responsive EoPs are higher in the blood of patients with allergic asthma compared with healthy control subjects 44 and that these cells are increased within the airways after allergen or IL-5 challenge in patients with atopic asthma, where the increase in EoP precedes the development of airway eosinophilia. 42,48,49 Consistent with these findings, the current study demonstrated that EoP numbers are increased in the blood and airways of patients with severe compared with mild asthma.…”

Type 2 Cytokine Responses: Regulating Immunity to Helminth Parasites and Allergic Inflammation

“…Conversely, hematopoietic progenitor cells are progeny of hematopoietic stem cells, but unlike stem cells, have limited self-renewal capacity and restricted lineage potential. CD34, a surface marker often used to identify hematopoietic stem/progenitor cells (HSPCs), is downregulated as HSPCs mature with the exception of some mast cells (5). HSPCs are mainly present in a specialized bone marrow niche that regulates their survival, proliferation, self-renewal and differentiation (5).…”

“…CD34, a surface marker often used to identify hematopoietic stem/progenitor cells (HSPCs), is downregulated as HSPCs mature with the exception of some mast cells (5). HSPCs are mainly present in a specialized bone marrow niche that regulates their survival, proliferation, self-renewal and differentiation (5). Hematopoiesis typically occurs in the bone marrow in response to signals received from stromal cells and growth factors.…”

“…Hematopoiesis typically occurs in the bone marrow in response to signals received from stromal cells and growth factors. However, differentiation does occur in peripheral tissues by a process called in situ hematopoiesis that is an important innate effector mechanism in T H 2 inflammation (5). Under homeostatic conditions, HSPCs leave the bone marrow and circulate in the bloodstream but their egress is increased in response to inflammatory signals.…”

“…Type 2 immune responses involve the cooperative actions of epithelial cells, dendritic cells (DCs), basophils, mast cells, eosinophils, type 2 innate lymphoid cells (ILC2s), alternatively activated M2 macrophages, T H 2 cells and IgE-producing B cells. In addition to these terminally differentiated cell types, there is also a growing appreciation for the role that hematopoietic stem/progenitor cells (HSPCs) play in promoting and maintaining type 2 inflammation(5). …”