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CD40L-expressing CD4 + T cells prime adipose-derived stromal cells to produce inflammatory chemokines.
- Source :
-
Cytotherapy [Cytotherapy] 2022 May; Vol. 24 (5), pp. 500-507. Date of Electronic Publication: 2022 Feb 23. - Publication Year :
- 2022
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Abstract
- The therapeutic potential of culture-adapted adipose-derived stromal cells (ASCs) is largely related to their production of immunosuppressive factors that are inducible in vitro by priming with inflammatory stimuli, in particular tumor necrosis factor-α (TNFα) and interferon-γ (IFNγ). In vivo, obesity is associated with chronic inflammation of white adipose tissue, including accumulation of neutrophils, infiltration by IFNγ/TNFα-producing immune cells, and ASC dysfunction. In the current study, we identified in obese patients a simultaneous upregulation of CD40Lin the adipose tissue stroma vascular fraction (AT-SVF), correlated with the Th1 gene signature, and an overexpression of CD40 by native ASCs. Moreover, activated CD4 <superscript>+</superscript> T cells upregulated CD40 on culture-expanded ASCs and triggered their production of IL-8 in a CD40L-dependent manner, leading to an increased capacity to recruit neutrophils. Finally, activation of ASCs by sCD40L or CD40L-expressing CD4 <superscript>+</superscript> T cells relies on both canonical and non-canonical NF-κB pathways, and IL-8 was found to be coregulated with NF-κB family members in AT-SVF. These data identify the CD40-CD40L axis as a priming mechanism of ASCs, able to modulate their cross talk with neutrophils in an inflammatory context, and their functional capacity for therapeutic applications.<br />Competing Interests: Conflict-of-interest Disclosure Authors have no competing interests to declare.<br /> (Copyright © 2022 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.)
Details
- Language :
- English
- ISSN :
- 1477-2566
- Volume :
- 24
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Cytotherapy
- Publication Type :
- Academic Journal
- Accession number :
- 35219585
- Full Text :
- https://doi.org/10.1016/j.jcyt.2022.01.006