Stem cell activity shapes the pleiotropic effects of IFN-γ and TGF-β in autoimmune diseases, infections, and cancer, and drives autoimmune flares and remissions

This study highlights the central role of stem cell activity in mediating the effects of IFN-γ and TGF-β1 on autoimmune diseases (AIDs), infections, and cancer, particularly in the context of autoimmune flares and remissions. It challenges the notion that immune privilege is an inherent feature of quiescent stem cells, showing instead that it depends on specific regulatory pathways. IFN-γ and TGF-β1 both induce stem cell quiescence but have opposite effects on immune privilege, with IFN-γ upregulating and TGF-β1 downregulating MHC-I expression. The study also notes that cytokines like IGF-1 and α-MSH, which enhance stem cell activity, downregulate MHC-I. The pleiotropic effects of these cytokines are linked to their influence on stem cell activity, which in turn affects the clinical outcomes of AIDs. High stem cell activity is associated with tissue regeneration and remission, while quiescence and tissue destruction lead to flares. The research suggests a TGF-β1 gradient between protected and less protected stem cell regions, facilitating both stem cell preservation and tissue regeneration.