Abstract
Innate lymphoid cells (ILCs) are increasingly acknowledged as important mediators of immune homeostasis and pathology. They act as early orchestrators of immunity and as such they make up interesting therapeutic targets for several diseases and possibly a means to peripheral tolerance. Taking advantage of an animal model of sterile peritonitis, induced by intraperitoneal injection of zymosan, a fungal derived TLR-2 ligand we studied the progenitor–successor relationship between the hematopoietic stem/progenitor cells (HSPC) and ILCs at the site of sterile inflammation. Our results demonstrate that the strength of the inflammatory signal affects the capacity of BM-derived HSPCs to migrate and give rise in situ to ILCs. Both low- and high-dose of zymosan injections triggered the appearance of mature ILCs in the peritoneal cavity. Only in low-dose injected mice, the recovered ILCs seemed to be dependent on an in situ differentiation of BM-derived HSPCs and/or ILC2 precursors (ILC2P) wherein high-dose, the stronger inflammatory environment seemed to be able to induce the emergence of ILCs independently of BM-derived HSPCs. To further elucidate the importance of the inflammatory environment per se for the attraction of mature ILCs, an anti- inflammatory drug was used. Treatment of mice with alpha-1 anti-trypsin (AAT) 15 min after injection of either low- or high- dose of zymosan, led to the blockade of the migration of HSPCs into the peritoneal cavity resulting in a loss of even mature ILCs in mice injected with the low-dose of zymosan. Contrary, in mice injected with high-dose, progenitor cells of type 2 of ILCs could be still recovered, but not mature ILC2 cells. We suggest that the relationship between HSPCs and ILCs seem to be affected by the strength of the inflammatory stimuli and that the use of anti-inflammatory molecules like A1 antitrypsin may attenuate the inflammation and to some extent prevent the migration of HSCPs to the site of inflammation and the emergence of mature ILCs.
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]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
