Mesenchymal stem cells inhibit Th17 cell differentiation by IL-10 secretion

Qu, Xuebin; Liu, Xingxia; Chen, Kai; Yang, Rongcun; Zhao, Robert Chunhua

doi:10.1016/j.exphem.2012.05.006

Cited by 98 publications

(60 citation statements)

References 53 publications

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“…In the current studies, AHE exposure stimulated an increase in the T-reg population of both the spleen and lung; however, levels were not affected by MSC administration in either the acute or recurrent AHE models. This is consistent with the lack of MSC effects on IL-10 levels in BAL fluid or in conditioned media obtained from MLN mixed lymphocyte cultures but is contrary to reports that MSCs suppress Th17 differentiation of splenic T cells by secretion of soluble mediators including IL-10 [56][57][58].…”

Section: Discussionsupporting

confidence: 87%

Mesenchymal Stromal Cells Mediate Aspergillus Hyphal Extract-Induced Allergic Airway Inflammation by Inhibition of the Th17 Signaling Pathway

Lathrop

Brooks

Bonenfant

et al. 2014

Stem Cells Translational Medicine

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Systemic administration of mesenchymal stromal cells (MSCs) suppresses airway inflammation and methacholine-induced airway hyper-responsiveness (AHR) in mouse models of T helper cell (Th) type 2-mediated eosinophilic allergic airway inflammation (AAI); however, the efficacy of MSCs in mouse models of severe Th17-mediated neutrophilic AAI has not yet been demonstrated. We assessed MSC effects in a mouse model of mixed Th2/Th17 AAI produced by mucosal exposure to Aspergillus fumigatus hyphal extract (AHE). Following sensitization produced by oropharyngeal AHE administration, systemic (tail vein) administration of syngeneic MSCs on the first day of challenge significantly reduced acute AHR predominantly through reduction of Th17-mediated airway inflammation. In parallel experiments, MSCs also mitigated AHR when administered during recurrent challenge 10 weeks after initial sensitization and challenge through reduction in systemic Th17-mediated inflammation. Investigation into potential mechanistic actions of MSCs in this model demonstrated that although T regulatory cells were increased in all AHE-treated mice, MSC administration did not alter T regulatory cell numbers in either the acute or recurrent model. Differential induction of interleukin-17a secretion was observed in ex vivo restimulation of mediastinal lymph node mixed-cell cytokine analyses. Although the mechanisms by which MSCs act to decrease inflammation and AHR in this model are not yet fully elucidated, decrease in Th17-mediated airway inflammation appears to play a significant role. These results provide a basis for further investigations of MSC administration as a potential therapeutic approach for severe refractory neutrophilic asthma. STEM CELLS TRANSLATIONAL MEDICINE 2014;3:194-205

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Section: Discussionsupporting

confidence: 87%

Mesenchymal Stromal Cells Mediate Aspergillus Hyphal Extract-Induced Allergic Airway Inflammation by Inhibition of the Th17 Signaling Pathway

Lathrop

Brooks

Bonenfant

et al. 2014

Stem Cells Translational Medicine

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“…MSCs produce immunemodulatory molecules such as hepatocyte growth factor (HGF), TGF-B, and PGE2, which may enact these cellular effects [55] . MSCs have also been reported to inhibit TH17 development through various means, including inhibition with the effector molecules PGE2, a truncated peptide of C-C chemokine ligand-2 (CCL-2), IL-10, and PD-1/PD-L1 ligation [52,[60][61][62][63] . Importantly, MSCs must be pre-exposed to a combination of effector cytokines, including IFNγ and TNFα or IL-1β, in order to efficiently suppress T cell function [58] .…”

Section: Mechanisms Of Msc Suppression Of Adaptive Immune Cellsmentioning

confidence: 99%

Mesenchymal stem cells: Emerging mechanisms of immunomodulation and therapy

Glenn¹

2014

WJSC

360

304

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Mesenchymal stem cells (MSCs) are a pleiotropic population of cells that are self-renewing and capable of differentiating into canonical cells of the mesenchyme, including adipocytes, chondrocytes, and osteocytes. They employ multi-faceted approaches to maintain bone marrow niche homeostasis and promote wound healing during injury. Biomedical research has long sought to exploit their pleiotropic properties as a basis for cell therapy for a variety of diseases and to facilitate hematopoietic stem cell establishment and stromal reconstruction in bone marrow transplantation. Early results demonstrated their usage as safe, and there was little host response to these cells. The discovery of their immunosuppressive functions ushered in a new interest in MSCs as a promising therapeutic tool to suppress inflammation and down-regulate pathogenic immune responses in graft-versus-host and autoimmune diseases such as multiple sclerosis, autoimmune diabetes, and rheumatoid arthritis. MSCs produce a large number of soluble and membrane-bound factors, some of which inhibit immune responses. However, the full range of MSC-mediated immune-modulation remains incompletely understood, as emerging reports also reveal that MSCs can adopt an immunogenic phenotype, stimulate immune cells, and yield seemingly contradictory results in experimental animal models of inflammatory disease. The present review describes the large body of literature that has been accumulated on the fascinating biology of MSCs and their complex effects on immune responses.

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“…Moreover, authors had demonstrated that TNF-a is a pleiotropic cytokine with ability to change production of other cytokines from stem cells, by activation of NF-kB [40]. However, IL-10 has also been pointed out as a relevant cytokine to control the stem cell differentiation [41]. In fact, it has been demonstrated that IL-17-enriched microenvironment play a detrimental role in experimental models of inflammatory diseases and Th17 cells are a major contributor of autoimmune inflammation in various autoimmune diseases.…”

Section: Discussionmentioning

confidence: 97%