Fig. 6.

Mechanisms and hypothesis of ILC2 regulation by androgens in males mice. It has been shown that ILC2P in the bone marrow are reduced in males compared to females C57BL/6 mice. This was associated with a reduction of CD25 expression on male ILC2s which exhibited a reduction in spontaneous proliferation [4]. Accumulation of KLRG1⁺ ILC2 in the bone marrow of male mice was also reported [51]. PLZF⁺ ILC precursors accumulated in male bone marrow, suggesting that androgen may inhibit ILC2 development in the bone marrow by limiting the transition from ILCP to ILC2P [51]. Cephus et al. [54] showed that 5α-DHT treatment limited lung ILC2 numbers. In male mice, ILC2 had an increased expression of KLRG1 and ST2, whereas CD25 expression was diminished. This phenotype was associated with a reduction of lung inflammation upon allergen challenge, and a reduction of cytokine production by ILC2 in male mice, indicating that androgens may not only affect ILC2 development and maintenance in tissues, but also their function [54,82]. It has been suggested that IL-33 expression could be differentially regulated between female and male mice, with estrogens-dependent upregulation in female [50,54]. However, the sex bias in lung ILC2 numbers and phenotypic changes are not affected by IL-33 deficiency [82].