Human Mesenchymal Stem Cell Secretome Driven T Cell Immunomodulation Is IL-10 Dependent

Abstract

The Human Mesenchymal Stem Cell (hMSC) secretome has pleiotropic effects underpinning its therapeutic potential. hMSC serum-free conditioned media (SFCM) contains a variety of cytokines, with previous studies linking a changed secretome composition to physoxia. The Jurkat T cell model allowed the efficacy of SFCM vs. serum-free media (SFM) in the suppression of immunological aspects, including proliferation and polarisation, to be explored. Cell growth in SFM was higher [(21% O-2 = 5.3 x 10(5) +/- 1.8 x 10(4) cells/mL) and (2% O-2 = 5.1 x 10(5) +/- 3.0 x 10(4) cells/mL)], compared to SFCM [(21% O-2 = 2.4 x 10(5) +/- 2.5 x 10(4) cells/mL) and (2% O-2 = 2.2 x 10(5) +/- 5.8 x 10(3) cells/mL)]. SFM supported IL-2 release following activation [(21% O-2 = 5305 +/- 211 pg/mL) and (2% O-2 = 5347 +/- 327 pg/mL)] whereas SFCM suppressed IL-2 secretion [(21% O-2 = 2461 +/- 178 pg/mL) and (2% O-2 = 1625 +/- 159 pg/mL)]. Anti-inflammatory cytokines, namely IL-4, IL-10, and IL-13, which we previously confirmed as components of hMSC SFCM, were tested. IL-10 neutralisation in SFCM restored proliferation in both oxygen environments (SFM/SFCM+antiIL-10 similar to 1-fold increase). Conversely, IL-4/IL-13 neutralisation showed no proliferation restoration [(SFM/SFM+antiIL-4 similar to 2-fold decrease), and (SFM/SFCM+antiIL-13 similar to 2-fold decrease)]. Present findings indicate IL-10 played an immunosuppressive role by reducing IL-2 secretion. Identification of immunosuppressive components of the hMSC secretome and a mechanistic understanding of their action allow for the advancement and refinement of potential future cell-free therapies.