This is especially relevant when studying the immune system in hypertension because both the immune response and development of hypertension have been causally and independently linked to the microbiome. Finally, an important factor to consider when studying Rag1−/− mice (or other immunodeficient models) is the possibility that basal levels of T and B cells differ between mice since genetic efficiency varies from mouse to mouse. Accordingly, it may be prudent to establish immune cell criteria before experimentation, for example, inclusion of models only if< 2% of circulating CD45 cells are CD3 or CD20.

Another consideration often overlooked in Rag1−/− mice is that immune cells besides B and T lymphocytes are present and functionally active and may contribute variably to immune and inflammatory responses. Natural killer cells are derived from the same common lymphoid precursor as lymphocytes and are present in Rag1 KO animals. Innate lymphoid cells (ILC) are also from the lymphoid lineage and similar to natural killer cells, they do not have Rag1-mediated recombined antigen receptor. They are ubiquitously expressed in Rag1 KO mice and play an important role in cell-cell interaction of the immune system. This cell population is subgrouped according to the expression profile of transcription factors (ILC-1