A Boy Thing?

There is an interesting study in Cell Reports suggesting that the sex difference in asthma incidence in adult humans may be a consequence of the pubertal surge in testosterone (https://www.theguardian.com/society/2017/nov/28/testosterone-could-explain-why-asthma-is-more-common-in-women-than-men). In childhood, boys are more likely to develop this respiratory problem than girls but the situation is reversed at puberty, with the condition being twice as prevalent in women. The scientists involved in the study focused on a type of white blood cell, ILC2, that is produced in the bone marrow before lodging in many tissues including the lungs. When foreign proteins (such as pollen or house mite dust) enter the lungs, the ILC2 cells produce cytokines that promote anti-inflammatory immune responses (although there is evidence that there may be different sub-populations of ILC2 cells with varying responses to cytokines). Asthma may be regarded as an overly intense inflammatory reaction in the lungs to 'allergens'. The Cell Reports study used very small samples of adult human subjects but seemed to show that subjects with asthma had more ILC2 cells than non-asthmatic counterparts. No sex-differences in cell levels were seen in healthy subjects but asthmatic women had twice as many ILC2 cells than men with the condition. The researchers then turned to mice where lung samples and hormone manipulations can be carried out. Lung samples revealed that adult female mice had more ILC2 cells than males or younger mice of either sex. Castration in early life (removing the source of testosterone) resulted in male mice showing an expansion of ILC2 cells in lung tissue comparable with that seen in adult females. It consequently seems likely that testosterone has a 'dampening' effect on the development of lung ILC2 cells and this accounts for the decline in asthma incidence in men after puberty. The link between asthma and sex-steroids is, however, probably more complex than this and needs to consider the ILC2 sub-populations as well as other androgens and oestrogens.