Renal Intercalated Cells: Alien Cells Inside Us?

Mammalian renal intercalated cells are known for their role in acid secretion and acid–base control. Herein, we discuss the theoretical reasons behind their development based on published data, focusing on the characteristics of renal intercalated cell biology that are not common in eukaryotes and looking for explanations of their persistence throughout evolution. Moreover, we have traced these characteristics back phylogenetically to the simplest organisms. Intercalated cells have the following additional functions and attributes: 1. They contribute to kidney defense mechanisms in response to both infectious and non-infectious kidney damage. 2. Intercalated cells are energized by V-ATPases in a similar fashion to protozoa. 3. They possess T-antigens, commonly found in embryonic and cancer cells, which confer invasive abilities to these cells. 4. Their plasticity enables the regeneration of other epithelial cells. These observations indicate that renal intercalated cells may trace their origins back to amoeboid cells that originated from an evolutionary lineage including protists, or even the last eukaryote common ancestor (LECA). The theoretical framework presented herein supports the following two predictions: 1. Sponge amoebocytes possess membrane V-ATPase and are sensitive to bafilomycin, but not to ouabain. 2. Sponge amoebocytes—along with diploblasts (such as Xenacoelomorpha), cnidarians, worms, ionocytes, and the entire cell lineage containing V-ATPase, carbonic anhydrase, and anion exchangers (HCO3-/Cl-)—have innate immunity, cellular dedifferentiation, and regeneration capabilities.