Innate immune cells, including macrophages, are functionally affected by thyroid hormone (TH). Macrophages can undergo phenotypical alterations, shifting between pro-(M1) and anti-inflammatory (M2) profiles. Previous studies have established that increased TH concentrations shift macrophages into a more pro-inflammatory phenotype. Cellular TH concentrations are partially determined by TH transporters, cellular gateways facilitating bidirectional TH transport that include monocarboxylate transporters (MCT) Mct8 and Mct10.

We show here that T3, Mct8 and Mct10 affect murine bone marrow derived macrophage (BMDM) polarization. T3 responsive gene expression was decreased in BMDM depleted of T3, Mct10 knockout (Mct10KO) and knockout of both Mct8 and Mct10 (Mct8/10dKO), indicating a reduction of T3 availability compared to wild type (WT) and T3 treated cells. After polarization into an M1 phenotype (using LPS + IFNɣ), T3-depleted BMDM showed reduced surface marker expression of the pro-inflammatory marker CD80 and decreased expression of the M1 marker genes IL-1β and CD38. Mct8KO and Mct10KO BMDM were unchanged in their M1 profile, while Mct8/10dKO BMDM showed increased pro-inflammatory surface marker CD86 and increased IL-1β expression. After polarization into an M2 phenotype (using IL-4), BMDM depleted of T3 and Mct8KO had a higher percentage of BMDM expressing the M2 surface marker CD206. Expression of Arg1 and Egr2, both M2 marker genes, increased in BMDM without T3, while Egr2 decreased in Mct8KO BMDM.

In conclusion, a lack of T3 in BMDM has an inhibitory effect on M1 polarization and an enhancing effect on M2 polarization. However, Mct8KO or Mct10KO had other, opposite or no effects on polarization compared to T3-depleted BMDM. This suggests that these effects may be at least partially due to other functions of the Mct8 and Mct10 transporters and not solely a T3 effect. Altogether, our data suggests that intracellular T3 availability and presence of TH transporters affects macrophage function and emphasizes the complicated interplay between TH and the immune system.