Research output: Contribution to journal › Article › Academic › peer-review
Mesenchymal stromal cells stimulate the proliferation and IL-22 production of group 3 innate lymphoid cells. / van Hoeven, Vera; Munneke, J. Marius; Cornelissen, Anne S. et al.
In: Journal of immunology (Baltimore, Md., Vol. 201, No. 4, 2018, p. 1165-1173.Research output: Contribution to journal › Article › Academic › peer-review
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TY - JOUR
T1 - Mesenchymal stromal cells stimulate the proliferation and IL-22 production of group 3 innate lymphoid cells
AU - van Hoeven, Vera
AU - Munneke, J. Marius
AU - Cornelissen, Anne S.
AU - Omar, Said Z.
AU - Spruit, Melchior J.
AU - Kleijer, Marion
AU - Bernink, Jochem H.
AU - Blom, Bianca
AU - Voermans, Carlijn
AU - Hazenberg, Mette D.
PY - 2018
Y1 - 2018
N2 - Infusion of mesenchymal stromal cells (MSCs) is a promising and increasingly applied therapy for patients who suffer from a variety of inflammatory diseases, including graft-versus-host disease (GvHD), a common and life-threatening complication after allogeneic hematopoietic stem cell transplantation. The therapeutic effect of MSCs is mainly ascribed to their ability to suppress T cells and to support tissue repair. However, clinical response rates in patients with GvHD are limited to 50%, and the determinants for MSC responsiveness are unknown.We recently reported that high frequencies of activated group 3 innate lymphoid cells (ILC3s) before and after allogeneic hematopoietic stem cell transplantation were associated with a lower risk of GvHD. This may be related to IL-22 production by ILC3s, a cytokine important for intestinal epithelial cell homeostasis. In this study, we investigated whether ILC3s may contribute to the therapeutic effect of MSCs by studying the interaction between MSCs and ILC3s in vitro. ILC3s isolated from human tonsils were cocultured with human bone marrow-derived MSCs for 5 d in the presence of IL-2. Coculture with MSCs enhanced the proliferation and IL-22 production of ILC3s. Reciprocally, ILC3s promoted ICAM-1 and VCAM-1 expression on MSCs. For both directions, the activation was mainly mediated by cell-cell contact and by MSC-derived IL-7 and likely by aryl hydrocarbon receptor ligands. Thus, in addition to inhibiting the proliferation of alloreactive T cells, MSCs also promote the expansion and IL-22 production of ILC3s, which may contribute to healthy homeostasis and wound repair in the treatment of various inflammatory conditions in the intestine, including GvHD.
AB - Infusion of mesenchymal stromal cells (MSCs) is a promising and increasingly applied therapy for patients who suffer from a variety of inflammatory diseases, including graft-versus-host disease (GvHD), a common and life-threatening complication after allogeneic hematopoietic stem cell transplantation. The therapeutic effect of MSCs is mainly ascribed to their ability to suppress T cells and to support tissue repair. However, clinical response rates in patients with GvHD are limited to 50%, and the determinants for MSC responsiveness are unknown.We recently reported that high frequencies of activated group 3 innate lymphoid cells (ILC3s) before and after allogeneic hematopoietic stem cell transplantation were associated with a lower risk of GvHD. This may be related to IL-22 production by ILC3s, a cytokine important for intestinal epithelial cell homeostasis. In this study, we investigated whether ILC3s may contribute to the therapeutic effect of MSCs by studying the interaction between MSCs and ILC3s in vitro. ILC3s isolated from human tonsils were cocultured with human bone marrow-derived MSCs for 5 d in the presence of IL-2. Coculture with MSCs enhanced the proliferation and IL-22 production of ILC3s. Reciprocally, ILC3s promoted ICAM-1 and VCAM-1 expression on MSCs. For both directions, the activation was mainly mediated by cell-cell contact and by MSC-derived IL-7 and likely by aryl hydrocarbon receptor ligands. Thus, in addition to inhibiting the proliferation of alloreactive T cells, MSCs also promote the expansion and IL-22 production of ILC3s, which may contribute to healthy homeostasis and wound repair in the treatment of various inflammatory conditions in the intestine, including GvHD.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85051267824&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/29980610
U2 - 10.4049/jimmunol.1700901
DO - 10.4049/jimmunol.1700901
M3 - Article
C2 - 29980610
VL - 201
SP - 1165
EP - 1173
JO - Journal of immunology (Baltimore, Md.
JF - Journal of immunology (Baltimore, Md.
SN - 0022-1767
IS - 4
ER -
ID: 5643735