Group 2 innate lymphoid cells support hematopoietic recovery under stress conditions

Abstract

The cell-cycle status of hematopoietic stem and progenitor cells (HSPCs) becomes activated following chemotherapy-induced stress, promoting bone marrow (BM) regeneration; however, the underlying molecular mechanism remains elusive. Here we show that BM-resident group 2 innate lymphoid cells (ILC2s) support the recovery of HSPCs from 5-fluorouracil (5-FU)–induced stress by secreting granulocyte-macrophage colony-stimulating factor (GM-CSF). Mechanistically, IL-33 released from chemo-sensitive B cell progenitors activates MyD88-mediated secretion of GM-CSF in ILC2, suggesting the existence of a B cell–ILC2 axis for maintaining hematopoietic homeostasis. GM-CSF knockout mice treated with 5-FU showed severe loss of myeloid lineage cells, causing lethality, which was rescued by transferring BM ILC2s from wild-type mice. Further, the adoptive transfer of ILC2s to 5-FU–treated mice accelerates hematopoietic recovery, while the reduction of ILC2s results in the opposite effect. Thus, ILC2s may function by “sensing” the damaged BM spaces and subsequently support hematopoietic recovery under stress conditions.

The bacterial microbiota regulates normal hematopoiesis via metabolite-induced type 1 interferon signaling

“…43 However, it is possible that non-myeloid mature blood cells such as innate lymphoid type 2 cells (ILC2) may also contribute to regulation of the hematopoietic compartment in a STAT1-dependent manner and further studies are necessary to define the contributions of these cells. 49 We found that stimulating NOD1, but not NOD2, promotes hematopoiesis in the absence of the microbiota in a STAT1-dependent manner. These data clarify previous reports that identified multiple innate immune pathways, including NOD1 and STAT1, as separately promoting hematopoiesis in a microbiota-dependent manner.…”

Type 2 Diabetes Mellitus and Latent Tuberculosis Infection Moderately Influence Innate Lymphoid Cell Immune Responses in Uganda

“…ILC2 production of type 2 cytokines that results in AAMs recruitment (19,57) may be considered detrimental in controlling Mtb. This may be contradictory as Sudo et al (58) reported that ILC2s produce GM-CSF, a cytokine known to activate macrophages and control Mtb infection (59). This may explain the slight increase in the ILC2 and IL-13 levels in the LBTI group.…”

Alveolar macrophages strictly rely on GM-CSF from alveolar epithelial type 2 cells before and after birth

“…It is possible that ILC2s create local tissue microenvironments that are enriched for GM-CSF and provide context-dependent support for particular myeloid compartments, such as eosinophils or DCs. Indeed, bone marrow ILC2s were recently reported to increase GM-CSF expression and to support hematopoietic recovery under conditions of stress hematopoiesis following treatment with 5fluorouracil (Sudo et al, 2021). Further studies are thus required to reveal the more subtle consequences of lung hematopoietic Csf2-deficiency with the necessary spatial resolution.…”