Understanding Sex-based Differences In Immune System Function

Many diseases impact men and women differently. Asthma tends to onslaught men earlier successful life, yet much women create asthma arsenic they get older. Parkinson's is much communal successful men, but Alzheimer's is much communal successful women. 

The differences are moreover much stark erstwhile it comes to autoimmune disease. Women are astir 2 and a half times much apt than men to create aggregate sclerosis and 9 times much apt to create lupus.

Why would immoderate diseases onslaught 1 activity much than another? And why do immoderate tissues, specified arsenic nan lungs and brain, look particularly susceptible to these sex-based differences?

To reply these questions, scientists astatine La Jolla Institute for Immunology (LJI) are starring caller investigation into really our immune cells take sides circumstantial parts of nan body.

In a caller Science review, LJI Professor, President & CEO Erica Ollmann Saphire, Ph.D., MBA, and LJI Associate Professor Sonia Sharma, Ph.D., analyse really genetics, activity hormones, and biology factors travel together to style nan immune system.

In conscionable nan past 2 years, LJI scientists person uncovered a full caller assemblage of accusation astir really nan immune systems of men and women are very different. We're looking astatine what is genetically encoded successful our XX aliases XY chromosomes, and really hormones for illustration estrogen and testosterone impact what is genetically programmed into our immune cells."

Erica Ollmann Saphire, Ph.D., MBA, LJI Professor, President & CEO 

In nan paper, nan researchers specify biologic activity (in an immunology context) arsenic nan beingness of XX chromosomes successful females and XY chromosomes successful males. "Every compartment successful your assemblage is either XX aliases XY," says Saphire. "That X chromosome has many, galore immune-related genes. Women person 2 copies of each. That gives them, successful a sense, doubly nan palette of colors to overgarment from successful formulating an immune response. It tin besides springiness them a stronger immune consequence for those genes that are doubly progressive - progressive successful some copies simultaneously.

Sex hormones are important for overmuch much than reproductive function. Immune cells tin besides consciousness hormones specified arsenic estrogen and testosterone and usage them to find which genes to move connected aliases disconnected and which ones to move connected much brightly aliases dim. This intends akin immune cells tin do different things, depending connected whether that compartment is from a antheral aliases a female. 

Further, female cells alteration successful which of their 2 copies of X is "turned on." As a result, women person organs pinch a collage, aliases mosaic, of immune cells that activity otherwise successful different tissues. This innate "variety" of immune cells appears to beryllium an effective measurement to ward disconnected infectious illness (women are amended than men astatine fighting disconnected pathogens specified arsenic SARS-CoV-2). 

But scientists person besides recovered that having much genes from X chromosomes whitethorn predispose women to autoimmune disease. This accrued X chromosome "dosage" is intimately linked to a higher consequence for autoimmune diseases specified arsenic Sjögren's syndrome and scleroderma.

New investigation into sex-based immune strategy differences is besides captious for processing caller crab immunotherapies, Sharma explains.

"We're progressively knowing really sex-based differences impact illness outcomes. When it comes to medicine, 1 size doesn't fresh everybody," says Sharma, who directs LJI's Center for Sex-Based Differences successful nan Immune System. "This is starring to caller research, peculiarly successful nan crab field, toward precision medicine. We're asking really a person's individual immune strategy is contributing to controlling that crab done immunotherapy."

Saphire and Sharma besides item biology factors, specified arsenic nutrition and chemic exposures, that whitethorn adhd to nan analyzable interplay of chromosomes and activity hormones. Men and women besides look to person immoderate signature differences successful their tegument and gut microbiomes.

The researchers dream these foundational discoveries tin lead to aesculapian advances for all, and they're moving pinch collaborators crossed nan state to move this investigation forward. "It takes a squad to construe these findings," says Sharma.