TY - JOUR
T1 - IFN-γ differentially regulates subsets of Gr-1+CD11b+ myeloid cells in chronic inflammation
AU - Zhan, Xiaoxia
AU - Fang, Yimin
AU - Hu, Shengfeng
AU - Wu, Yongjian
AU - Yang, Kun
AU - Liao, Chunxin
AU - Zhang, Yuanqing
AU - Huang, Xi
AU - Wu, Minhao
N1 - Publisher Copyright:
© 2015 Elsevier Ltd.
PY - 2015/8/1
Y1 - 2015/8/1
N2 - During chronic inflammation, prolonged over-reactive immune response may lead to tissue destruction, while immune suppression hinders tissue repair and pathogen elimination. Therefore, precise regulation of the immune response is needed to avoid immuno-pathology. Interferon-gamma (IFN-γ) is widely used in clinical treatment of inflammatory diseases. However, the underlying mechanism remains unclear. Here, we evaluated the role of IFN-γ on CD11b+Gr-1+ myeloid cell differentiation and function, using a heat-killed Mycobacterium bovis BCG-induced chronic inflammation model. After challenge with heat-killed BCG, two subpopulations of CD11b+Gr-1+ myeloid cells were generated in the mouse spleen. Phenotypical, morphological and functional analysis indicated that the CD11b+Gr-1high Ly6Ghigh Ly6Clow subset was neutrophil-like myeloid-derived inducer cells (N-MDICs), which promoted T cell activation, while the other subset was CD11b+Gr-1low Ly6Gneg Ly6Chigh monocyte-like myeloid-derived suppressor cells (M-MDSCs) that displayed extensive suppressor function. IFN-γ treatment dampened N-MDICs-mediated T cell activation through up-regulating T cell suppressive mediators, reactive oxygen species (ROS) and arginase I. While for M-MDSCs, IFN-γ reduced their suppressing activity by decreasing the arginase activity. Our study provides evidence that IFN-γ balances the over-reactive vs compromised immune response through different regulation of distinct myeloid subsets, and therefore displays significant therapeutic potential for effective immuno-therapy of chronic inflammatory diseases.
AB - During chronic inflammation, prolonged over-reactive immune response may lead to tissue destruction, while immune suppression hinders tissue repair and pathogen elimination. Therefore, precise regulation of the immune response is needed to avoid immuno-pathology. Interferon-gamma (IFN-γ) is widely used in clinical treatment of inflammatory diseases. However, the underlying mechanism remains unclear. Here, we evaluated the role of IFN-γ on CD11b+Gr-1+ myeloid cell differentiation and function, using a heat-killed Mycobacterium bovis BCG-induced chronic inflammation model. After challenge with heat-killed BCG, two subpopulations of CD11b+Gr-1+ myeloid cells were generated in the mouse spleen. Phenotypical, morphological and functional analysis indicated that the CD11b+Gr-1high Ly6Ghigh Ly6Clow subset was neutrophil-like myeloid-derived inducer cells (N-MDICs), which promoted T cell activation, while the other subset was CD11b+Gr-1low Ly6Gneg Ly6Chigh monocyte-like myeloid-derived suppressor cells (M-MDSCs) that displayed extensive suppressor function. IFN-γ treatment dampened N-MDICs-mediated T cell activation through up-regulating T cell suppressive mediators, reactive oxygen species (ROS) and arginase I. While for M-MDSCs, IFN-γ reduced their suppressing activity by decreasing the arginase activity. Our study provides evidence that IFN-γ balances the over-reactive vs compromised immune response through different regulation of distinct myeloid subsets, and therefore displays significant therapeutic potential for effective immuno-therapy of chronic inflammatory diseases.
KW - Chronic inflammation
KW - IFN-γ
KW - Myeloid-derived suppressor cells
KW - Neutrophil-like myeloid-derived inducer cells
UR - http://www.scopus.com/inward/record.url?scp=84937974198&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84937974198&partnerID=8YFLogxK
U2 - 10.1016/j.molimm.2015.05.011
DO - 10.1016/j.molimm.2015.05.011
M3 - Article
C2 - 26021804
AN - SCOPUS:84937974198
SN - 0161-5890
VL - 66
SP - 451
EP - 462
JO - Molecular Immunology
JF - Molecular Immunology
IS - 2
ER -