Adhesive substrate-modulation of adaptive immune responses

Abhinav P. Acharya, Natalia V. Dolgova, Michael J. Clare-Salzler, Benjamin G. Keselowsky

Research output: Contribution to journalArticlepeer-review

56 Scopus citations

Abstract

While it is well-known that adsorbed proteins on implanted biomaterials modulate inflammatory responses, modulation of dendritic cells (DCs) via adhesion-dependent signaling has only been begun to be characterized. In this work, we demonstrate that adhesive substrates elicit differential DC maturation and adaptive immune responses. We find that adhesive substrates support similar levels of DC adhesion and expression of stimulatory and co-stimulatory molecules. Conversely, DC morphology and differential production of pro- and anti-inflammatory cytokines (IL-12p40 and IL-10, respectively) is adhesive substrate-dependent. For example, DCs cultured on collagen and vitronectin substrates generate higher levels of IL-12p40, whereas DCs cultured on albumin and serum-coated tissue culture-treated substrates produce the higher levels of IL-10 compared to other substrates. Additionally, our results suggest substrate-dependent trends in DC-mediated allogeneic CD4+ T-cell proliferation and T-helper cell type responses. Specifically, we show that substrate-dependent modulation of DC IL-12p40 cytokine production correlates with CD4+ T-cell proliferation and Th1 type response in terms of IFN-γ producing T-helper cells. Furthermore, our results suggest substrate-dependent trends in DC-mediated stimulation of IL-4 producing T-cells, but this Th2 type response is not dependent on DC production of IL-10 cytokine. This work has impact in the rational design of biomaterials for diverse applications such as tissue-engineered constructs, synthetic particle-based vaccines and the ex vivo culture of DCs for immunotherapies.

Original languageEnglish (US)
Pages (from-to)4736-4750
Number of pages15
JournalBiomaterials
Volume29
Issue number36
DOIs
StatePublished - Dec 1 2008
Externally publishedYes

Keywords

  • Cell adhesion
  • Extracellular matrix (ECM)
  • Immune response
  • Immunomodulation
  • Inflammation
  • Integrin

ASJC Scopus subject areas

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

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