Open AccessMesenchymal stromal cells of the bone marrow and natural killer cells: cell interactions and cross modulation
Author(s) -
Najar Mehdi,
FayyadKazan Mohammad,
Meuleman Nathalie,
Bron Dominique,
FayyadKazan Hussein,
Lagneaux Laurence
Publication year - 2018
Publication title -
journal of cell communication and signaling
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.329
H-Index - 44
eISSN - 1873-961X
pISSN - 1873-9601
DOI - 10.1007/s12079-018-0448-4
Subject(s) - mesenchymal stem cell , granzyme , bone marrow , stromal cell , interleukin 12 , cytotoxic t cell , microbiology and biotechnology , cell therapy , perforin , lymphokine activated killer cell , immunology , interleukin 21 , cancer research , biology , immune system , stem cell , t cell , cd8 , in vitro , biochemistry
Bone marrow‐derived mesenchymal stromal cells (BM‐MSCs) are multipotent progenitor cells that have shown promise for several different therapeutic applications. As they are able to modulate the function of several types of immune cells, BM‐MSCs are highly important in the field of cell‐based immunotherapy. Understanding BM‐MSC‐natural killer (NK) cell interactions is crucial for improving their therapeutic efficiency. Here, we observed that the type of NK cell‐activating cytokine (e.g., IL‐2, IL‐12, IL‐15 and IL‐21) strongly influenced the outcomes of their interactions with BM‐MSCs. The expression patterns of the ligands (CD112, CD155, ULPB‐3) and receptors (LAIR, NCR) mediating the cross‐talk between BM‐MSCs and NK cells were critically modulated following co‐culture. BM‐MSCs partially impaired NK cell proliferation but up‐regulated their secretion of IFN‐γ and TNF‐α. As they are cytotoxic, activated NK cells induced the killing of BM‐MSCs. Indeed, BM‐MSCs triggered the degranulation of NK cells and increased their release of perforin and granzymes. Interestingly, activated NK cells induced ROS generation within BM‐MSCs that caused their decreased viability and reduced expression of serpin B9. Collectively, our observations reveal that BM‐MSC‐NK cell interactions may impact the immunobiology of both cell types. The therapeutic potential of BM‐MSCs will be significantly improved once these issues are well characterized.