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Mammary gland is shaped by adaptive immune system during development

In experiments with mouse tissue, UC San Francisco researchers have discovered that the adaptive immune system, generally associated with fighting bacterial and viral infections, plays an active role in guiding the normal development of mammary glands, the only organs–in female humans as well as mice–that develop predominately after birth, beginning at puberty.

The scientists say the findings have implications not only for understanding normal organ development, but also for cancer and tissue-regeneration research, as well as in the highly active field of cancer immunotherapy, which seeks to develop drugs that prompt the adaptive immune system to attack tumor cells.

“It’s essential that we pay attention to how normal development unfolds, because regeneration requires reigniting developmental processes, and cancer can be thought of as ‘development gone wrong,’” said senior author Zena Werb, PhD, professor and vice-chair of anatomy at UCSF and co-leader of the Cancer, Immunity and Microenvironment Program at the UCSF Helen Diller Family Comprehensive Cancer Center.

Previous research has shown that the innate immune system, a suite of evolutionarily ancient, general-purpose defenses that is fully operational before birth, helps to orchestrate the development of several organs both pre- and postnatally. The adaptive immune system, which springs into action after birth to continually create customized antibodies over a lifetime to protect us against the pathogens we encounter, also is known to influence the development of immune system organs such as the thymus, spleen and lymph nodes.

But the new discoveries, published online in Developmental Cell on Aug. 27, 2015, break new ground by demonstrating that the adaptive immune system can play a conducive role in the postnatal development of organs not directly involved in immunity, said first author Vicki Plaks, PhD, a postdoctoral fellow in the Werb laboratory who led the new research.

The mouse mammary gland is an excellent model to study these processes – it develops “from almost nothing to everything” in about four weeks, said Plaks, and matures roughly in parallel with adaptive immunity – but the researchers said that the findings may also apply to the prostate gland, skin, and gut, all of which undergo postnatal structural changes.

Mice have 10 mammary glands, which consist of a structure known as a fat pad that, at birth, contains a rudimentary stalk of cells called epithelial cells. At puberty, an explosive growth process known as “ductal invasion” takes place within each gland: epithelial cells rapidly and extensively proliferate throughout the fat pad in a complex branching pattern, forming a series of tubes that connect with a hollow space called the lumen, through which milk will eventually flow to the nipple.