Testos­terone could ex­plain why asthma is more com­mon in women than men

The Guardian Australia - - Science - Nicola Davis

The puz­zle of why asthma is about twice as com­mon in women as men may have been solved, ac­cord­ing to re­searchers who say it might partly be down to testos­terone.

While boys are about 1.5 times as likely to have asthma as girls, the sit­u­a­tion changes with ado­les­cence – a fac­tor that has led sci­en­tists to probe whether sex hor­mones could be be­hind the trends.

To un­pick pos­si­ble mech­a­nisms be­hind the gen­der dif­fer­ences, a team of re­searchers from the US fo­cused on a type of white blood cells, known as ILC2 cells, that orig­i­nate in the bone mar­row and be­come “seeded” in par­tic­u­lar tis­sues of the body, in­clud­ing the lungs, early in life.

When an al­ler­gen en­ters the lungs, the cells lin­ing the air­ways se­crete pro­teins which in turn trig­ger ILC2 to ex­pand and pro­duce yet more pro­teins, which kick off a cas­cade of in­flam­ma­tory re­sponse.

“We were in­ter­ested in de­ter­min­ing whether or not sex hor­mones reg­u­late th­ese cells, since they are im­por­tant in ini­ti­at­ing the in­flam­ma­tory re­sponse and so lit­tle is known about them,” said Dr Dawn New­comb, co-au­thor of the re­search from Van­der­bilt Univer­sity.

New­comb and col­leagues be­gan by look­ing at the lev­els of ILC2 cells in the blood of a group of four healthy men and four healthy women, as well as six women and seven men with asthma.

The find­ings, pub­lished in the jour­nal Cell Re­ports, re­vealed in­di­vid­u­als with asthma had higher lev­els of ILC2 cells than those with­out. More­over, while there was lit­tle dif­fer­ence in lev­els of the cells for healthy par­tic­i­pants, women with asthma had about twice the lev­els of ILC2 cells com­pared with men with the con­di­tion.

The team then turned to mice, and found that adult fe­males had more ILC2 cells in their lung tis­sue than males or young mice of ei­ther sex.

They then car­ried out a se­ries of ex­per­i­ments ma­nip­u­lat­ing hor­mone lev­els in mice and prob­ing the im­pact on ILC2 cells. Among their stud­ies, the team com­pared the sit­u­a­tion be­tween mice with sex hor­mones present in their bod­ies, and those who had had their testes or ovaries re­moved early in life. “What we found is that the mice that lacked testos­terone had sig­nif­i­cantly more ILC2 ex­pan­sion and func­tion com­pared to the male mice that had testos­terone,” said New­comb.

To­gether, the re­sults sug­gest that testos­terone is im­por­tant in damp­en­ing the ex­pan­sion and pro­tein pro­duc­tion from the ILC2 cells in the lungs, keep­ing the im­mune re­sponse in check.

Dr Do­minick Shaw, se­vere asthma lead at the Univer­sity of Not­ting­ham who was not in­volved in the study, wel­comed the re­search.

“It ap­pears testos­terone and oe­stro­gen change this in­flam­ma­tory path­way in dif­fer­ent ways within mouse lungs. Now mice are a long way from pa­tients … but it is plau­si­ble,” he said, not­ing that more women than men have se­vere asthma, and changes in asthma symp­toms have been linked to the men­strual cy­cle. “What is in­ter­est­ing about th­ese data is it starts to drill down into what the sex hor­mones might be do­ing in terms of the asthma mech­a­nisms.”

Shaw said the study adds weight to re­cent ef­forts by phar­ma­ceu­ti­cal com­pa­nies to tar­get par­tic­u­lar pro­teins in­volved in asthma, and that the work sug­gests it could be ben­e­fi­cial to tar­get pro­teins pro­duced by ILC2 cells.

“For many years asthma has been seen as a sim­ple di­ag­no­sis, and you just give steroids. What we have re­alised over the last five or 10 years is that it is a highly com­plex di­ag­no­sis and dif­fer­ent peo­ple have dif­fer­ent types of asthma, so we are try­ing to per­son­alise the treat­ments to in­di­vid­u­als with asthma,” he said. “What this pa­per sug­gests is that there might be dif­fer­en­tial re­sponses based on gen­der to some of those drugs [com­ing] in the fu­ture.”

When an al­ler­gen en­ters the lungs, the cells lin­ing the air­ways se­crete pro­teins which trig­ger a type of white blood cell to pro­duce more pro­teins, which start a cas­cade of in­flam­ma­tory re­sponse. Pho­to­graph: Yui Mok/PA

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