Mesenchymal Stem Cells Induce Functionally Active T-Regulatory Lymphocytes in a Paracrine Fashion and Ameliorate Experimental Autoimmune Uveitis

Tasso, Roberta; Ilengo, Cristina; Quarto, Rodolfo; Cancedda, Ranieri; Caspi, Rachel R; Pennesi, Giuseppina

doi:10.1167/iovs.11-8211

Cited by 90 publications

(56 citation statements)

References 40 publications

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“…Immunogens investigated in models include sensitization and challenge with ovalbumin, ragweed pollen, dust mite antigen, and toluene diisocyanate, and comparable effects have been observed with syngeneic, allogeneic, or xenogeneic MSC administration. Postulated mechanisms of MSC actions include a shift from Th2 to Th1 antigen-specific CD4 T cells and an increase in T regulatory cells (T-regs) [31,36,39]. These results suggest that MSCs may be effective in clinical asthma.…”

Section: Introductionmentioning

confidence: 97%

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: Introductionmentioning

confidence: 97%

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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“…Additionally, systemic administration of MSCs in mice has been shown to attenuate experimental autoimmune uveitis. 17 In an experimental model of choroidal neovascularization, intravenously injected MSCs were specifically recruited to the lesion site. 18 MSCs have also been shown to preserve the photoreceptors in Royal College Surgeon (RCS) rats and in rats with diabetic retinopathy.…”

Section: Discussionmentioning

confidence: 99%

Stromal Cell-Derived Factor 1α-Stimulated Mesenchymal Stem Cells Confer Enhanced Protection Against Light-Induced Retinal Degeneration in Rats

Wang

et al. 2013

Current Eye Research

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“…Foxp3 ? Treg cells (Tasso et al 2012). On the other hand, cell contacts play an important role in the MSCs' interaction with this T-reg subpopulation.…”

Section: Cell-to-cell/paracrine Interactionsmentioning

confidence: 99%

Factors governing the immunosuppressive effects of multipotent mesenchymal stromal cells in vitro

2015

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Multipotent mesenchymal stem/stromal cells (MSCs) are of great interest to researchers because of the unique properties, such as enhanced proliferation, paracrine activity and multilineage differentiation. Their non-immunogenicity, in combination with immunomodulatory properties, opens up the opportunity for the allogeneic application of MSCs. The MSC immunomodulatory capacity is currently being actively studied in vitro using various experimental designs. However, the results are not always univocal. It was found that the outcome of the stromal/immune cell interaction depends on experimental conditions. In this review we considered the impact of different factors, such as the ratio of stromal/immune cells, interaction time, the path of immune cell activation, etc. on the MSC immunomodulation. We also accentuated the importance of local milieu, in particular, oxygen tension, for the realization of MSC immunosuppressive activity.

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Mesenchymal Stem Cells Induce Functionally Active T-Regulatory Lymphocytes in a Paracrine Fashion and Ameliorate Experimental Autoimmune Uveitis

Abstract: The authors demonstrated that MSCs can inhibit EAU and that their immunomodulatory function is due at least in part to the induction of antigen-specific Treg in a paracrine fashion by secreting TGFβ.

Cited by 90 publications

References 40 publications

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

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

Stromal Cell-Derived Factor 1α-Stimulated Mesenchymal Stem Cells Confer Enhanced Protection Against Light-Induced Retinal Degeneration in Rats

Factors governing the immunosuppressive effects of multipotent mesenchymal stromal cells in vitro

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