CFTR corrector-mediated normalization of circulating S1P levels and a concomitant reduction of the frequency of S1P1+ immune cells in the spleen together with a lowering of pro-inflammatory monocytes and T-cells infiltrating the lung during HF support a role for S1P chemotaxis in HF-associated systemic and tissue inflammation. Here, MBTPS1 is linked to hydrops fetalis.