Effect of calcitriol on myeloid-derived suppressor cells in physiological aging

The active hormonal form of vitamin D, 1,25(OH)₂D, regulates many components of the immune system and previous research shows that 1,25(OH)₂D reduces the number and suppressive activity of MDSCs in tumors. This study aimed to evaluate the effects of calcitriol treatment on MDSCs in aged mice. We showed that aged BALB/c and CD1 mice exhibited increased levels of CD11b⁺Gr1⁺ cells in both the spleen and bone marrow compared to young mice. These cells displayed a less mature phenotype marked by reduced F4/80 expression and demonstrated robust T cell suppressive activity, as evidenced by their ability to inhibit the production of IFNγ and TNFα. Treatment of aged mice with calcitriol, administered twice weekly at a dose equivalent to 1 µg/kg for 4 weeks, significantly increased the population of CD11b⁺Gr1⁺ cells in the spleen, but not in the bone marrow of the animals, and promoted their differentiation into a more mature phenotype characterized by elevated F4/80 expression. In addition, calcitriol-treated aged mice exhibited significantly improved T cell responses, as indicated by increased IFNγ production upon specific antigen stimulation compared to the control group of mice. In vitro, calcitriol treatment of bone marrow-derived MDSCs similarly enhanced F4/80 expression without altering other markers such as CD11b, CD11c, or MHCII, and led to reduced expression of reactive oxygen species by these cells. Our study highlights the consistency of MDSC expansion across inbred and outbred mouse strains and supports the immunomodulatory role of calcitriol in promoting MDSC maturation and alleviating immune suppression in aging.