Abstract
Hematopoietic stem/progenitor cells (HSPC) are characterized by their unique capacities of self-renewal and multi-differentiation potential. This second property makes them able to adapt their differentiation profile depending on the local environment they reach. Taking advantage of an animal model of peritonitis, induced by injection of the TLR-2 ligand, zymosan, we sought to study the relationship between bone marrow-derived hematopoietic stem/progenitor cells (BM-HSPCs) and innate lymphoid cells (ILCs) regarding their emergence and differentiation at the site of inflammation. Our results demonstrate that the strength of the inflammatory signals affects the capacity of BM-derived HSPCs to migrate and give rise in situ to ILCs. Both low- and high-dose of zymosan injections trigger the appearance of mature ILCs in the peritoneal cavity where the inflammation occurs. Herein, we show that only in low-dose injected mice, the recovered ILCs are dependent on an in situ differentiation of BM-derived HSPCs and/or ILC2 precursors (ILC2P) wherein high-dose, the stronger inflammatory environment seems to be able to induce the emergence of ILCs independently of BM-derived HSPCs. We suggest that a relationship between HSPCs and ILCs seems to be affected by the strength of the inflammatory stimuli opening new perspectives in the manipulation of these early hematopoietic cells.
Highlights
Innate lymphoid cells (ILCs) arise from fetal progenitors or from common lymphoid progenitors (CLP) within the bone marrow
Knowing that hematopoietic stem/progenitor cells (HSPCs) migrate to inflamed tissues [17], we investigated whether mature innate lymphoid cells (ILCs) migrate directly to the inflammatory site or BM-Hematopoietic stem/progenitor cells (HSPC) differentiate in situ into ILCs
There was no significant difference in both frequency and total cell number of ILCs between the two groups of zymosan-treated mice (Figure 1B,C)
Summary
Innate lymphoid cells (ILCs) arise from fetal progenitors or from common lymphoid progenitors (CLP) within the bone marrow. Group 2 ILCs secrete Th2-related cytokines such as IL-4, IL-5, and IL-13 together with up-regulated expression of the transcription factor Gata-3 [4, 8,9,10]. Group 3 ILCs produce pro-inflammatory cytokines including IL-17, IL-21, IL-22, and GM-CSF and, express the transcription factor RORgt [11,12,13]. ILC1 and ILC3, but not ILC2, express retinoic acid and CCR7 homing receptors that are expressed by activated T cells. Upon activation, these receptors guide the migration of activated T cells to non-lymphoid tissues [14]. ILC2s use homing receptors, in common with myeloid and certain innate cells [14]
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