J. LEE NELSON LAB -- Research Overview
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Research Overview


“Your Cells Are My Cells.”
A New Paradigm in Human Health and Disease: Retained Cells from Pregnancy Exchange

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During pregnancy some cells traffic from mother to fetus and from fetus to mother. Surprisingly, some mother's cells are found in her adult offspring and some cells from the fetus are found in the mother decades later. Microchimerism (Mc) refers to harboring a small number of cells or DNA from a genetically different individual. The overall goal of our research group is to elucidate the consequences of Mc for human health.

Naturally acquired Mc from pregnancy is likely to provide benefits but also probably sometimes has adverse effects. We study both beneficial and detrimental effects of Mc primarily for autoimmune diseases and cancer.

We initially proposed that retained cells from pregnancy contribute to autoimmune diseases. Autoimmune diseases are thought of as disorders in which a body's cells inexplicably attack its own normal tissues.  The autoimmune diseases we study are scleroderma, rheumatoid arthritis, and multiple sclerosis. Anne Stevens, MD, PhD, who previously worked with us investigates Mc in systemic lupus erythematosus.

The new Mc model was conceived by combining observations from different medical subspecialties. One observation came from transplantation, which also results in chimerism. In hematopoietic cell (or bone marrow) transplantation the recipient can develop an illness that looks like autoimmune disease. Another observation also derives from transplantation and has to do with a group of molecules called human leukocyte antigens (HLA) that are key determinants of transplantation success.

HLA molecules are critical for distinguishing self from what non-self and are centrally important in immune responses. HLA matching of donor and recipient is the key determinant of success in transplantation. Interestingly, particular HLA genes (HLA class II) are associated with autoimmune diseases. By analogy, considering Mc we initially asked the question whether certain mother-child HLA-relationships predispose a woman to autoimmune disease. Our theory was that if persisting Mc from the fetus had excessive HLA similarity (but not complete identity) to the mother they could more easily interfere with the mother’s normal immune system balance.  

Scleroderma has a predilection for women and has a peak incidence in post reproductive years. Consistent with our hypothesis, children born to women who later developed scleroderma had excessive HLA (class II) sharing with their mothers compared to healthy controls. We further found higher levels of fetal origin Mc in women with scleroderma compared to healthy women. We are now investigating the mechanism by which these cells could contribute to scleroderma. If Mc is involved in the causation of scleroderma, or other autoimmune diseases, the cells could be selectively targeted for treatment. 

In other work we found that in addition to immune cells Mc is also present as specific types of cells in tissues. In heart tissue from children with neonatal lupus and heart block maternal cells in the heart muscle were heart muscle cells. This raises the question whether an “autoimmune” disease might occur due to loss of tolerance to natural immigrants such as maternal Mc in tissues. In the pancreas we found maternal insulin-producing cells including in type 1 diabetes. These cells could also be educational and/or contribute to attempts to repair disease-affected tissues.

On the beneficial side we recently tested the hypothesis that persisting fetal Mc might in part explain the protective effect of prior pregnancy on breast cancer risk. Consistent with this hypothesis, we found fetal Mc significantly less often in women with breast cancer compared to healthy women. We are currently investigating Mc of maternal origin as potentially potent against recurrent leukemia in patients who receive cord blood transplantation as treatment.

All individuals are subject to maternal Mc and women are also subject to fetal Mc from pregnancy. Overall the findings in this new field of research support replacement of the traditional paradigm that pits a separate self against others, by a paradigm that considers health and disease only after redefining "the self", including the naturally acquired Mc that is probably always with us. Embracing the new paradigm leads to intriguing questions and to new possibilities including whether adverse consequences of Mc could be ameliorated by targeted removal and whether beneficial effects of Mc could be harnessed for restorative purposes.

Images used with permission from Scientific American.

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