Bone marrow progenitors and IL-2 signaling contribute to the strain differences of kidney innate lymphoid cells

Innate lymphoid cells (ILCs) are critical mediators of immune responses by their robust production of cytokines. ILCs are mainly present in mucosal tissues, but their regulatory function in the kidney is attracting attention. Nevertheless, the understanding of their unique biology, compared to other tissues, is largely unknown.Here, we aimed to examine the effect of BALB/c and C57BL/6 strains on the number and function of kidney ILCs and their underlying mechanisms. Although the BALB/c strain showed an increase in ILC2 frequency than that of C57BL/6 in most organs, the difference in ILC2 frequency between the two strains was most pronounced in the kidney. These results were derived from increased ILC precursors in the bone marrow, and levels of renal Il2 in BALB/c mice. Furthermore, IL-2 receptor (CD25) expression and STAT5 phosphorylation also exaggerated in BALB/c kidney ILC2s. However, similar IL-2-dependent proliferation and activation of ILC2s were observed upon IL-2C treatment in both strains. Thus, homeostatic differences in kidney ILC2 number and function derive from differences in IL-2 signaling resulting from intrinsic and extrinsic factors. Together, we demonstrate previously unknown properties of kidney ILC2s based on their mice strain background and contributing factors. All these factors should be considered critical for the successful translation of immune diseases in experimental mouse models. Overall design: Comparative gene expression profiling analysis of RNA-seq data for kidney tissue from BALB/c mice (n=3), and C57BL/6 mice (n=3)