Emerging Questions in Materno-Fetal Microchimerism

Materno-fetal microchimerism is a common, life-long chimeric state first established by the exchange ofsmall numbers of cells between the motherand the fetus during pregnancy. This apparently trivial phenomenon is now attracting attention due to its unexpected andprofound implications in the immune system. For example, is the placenta really an immunological barrier? How do we balance the internal environment despite the existence of an immunological non-self? In this review, I will discuss the pros and cons of materno-fetal microchimerismforour immune system (e.g., tolerance, materno-fetal immune disease, tissue regeneration, etc.) and the unanswered, puzzling aspects of microchimerismfrom theimmunological point of view. Corresponding author: Naoki Irie, RIKEN Center for Developmental Biology, Laboratory for Evolutionary Morphology, Japan, E-mail: [email protected] Received September 28, 2011; Accepted November 16, 2011; Published November 18, 2011 Citation: Irie N (2011) Emerging Questions in Materno-Fetal Microchimerism. Reproductive Sys Sexual Disord S1:002. doi:10.4172/2161-038X.S1-002 Copyright: © 2011 Irie N, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. We are all chimeras consisting of self and non-self cells All of the billions of cells in our body come from a single fertilized egg. However, recent studies have revealed that cells from other people reside in our bodies. These are the cells of ourimmediate family members, ourmother, twins, or ourchildren in the case of parous women, exchanged during pregnancy. Surprisingly these cells are reported to last for more than a decade after birth [1]. Where are they located in our bodies? Various body organs and parts are known to possess non-self cells, including the skeletal muscles; heart; skin; lung; thyroid gland; digestive tube; liver; and even immunity-related organs such as the thymus, spleen, lymph nodes, peripheral blood, and bone marrow [2,3]. Even mouse brainshave beenfound to carry thecells of their children [4-6]. A body consisting of cells from 2 or more genetically distinct populations is called a chimera. Since the number of cells in pregnancyrelated chimera is relatively small (about 1 in 1000~10,000), the phenomenonis called “microchimerism” [7] (Figure 1). Meanwhile, despite their low frequency among our own cells, all people are considered to be in a microchimeric state, and parous womenare considered to have cells of more than 3different origins: their own cells, their mother’s cells, and those of their children [2]. Why have these cells come under the spotlight in the field of immunology? This review will describe recent advances and emerging questions in this field. How domicrochimeric cells pass through the placenta? Let us start with how microchimerism occurs. Although the precise timing of cell transfer remains to be clarified [8], microchimerism is establishedduring pregnancy [9,10]. A major question is how these maternal and fetal cells migratedfrom one body to the other. During pregnancy, the risk of immunological conflict (especially an attack by the maternal immune system) is avoided by the placenta, which filters various substances including immune cells. However, based on recent reports,the concept of the placenta as an immunological barrier is now being challenged. That is, fetal and maternal cells cross the placenta and engraft with each other, resulting in microchimerism [4,11]. How do microchimeric cells become accepted by the host’s immune system? How do host immune systems live with these non-self cells? Although the precise mechanism is still under investigation [4,12,13], the condition of the mother’s and infant’s immune systems seem to affect the number of cells that are exchanged. One factoris thesoundness of the immune systems of the mother and the fetus. For example, in infants with severe combined immunodeficiency disease (SCID), more cells migrate from the mother into the fetus [14]. Similar results were reported in a mouse model. Whenthe mother mouse was immunologically deficient (RAG -/-), the mother accepted more fetal cells [15]. These findings show that absence of a functional immune system results in the exchange of a greater number of cells compared to when the immune systems are healthy. Another factor that affects the degree of microchimerismis the immunological compatibility between the mother and the fetus. Based on reports from Berry et al.,maternofetal major histocompatibility complex (MHC)compatibility seemsto favor acceptance of maternal cells [16], albeit this trend was not reproduced in a certain mouse model [17]. Together, these findings suggest that microchimeric cells are not cells that accidentally crossed the placenta, but are proportions of Figure 1: Materno-fetal microchimerism established during pregnancy. During pregnancy, exchange of small numbers of maternal and fetal cells occurs by an unknown mechanism (possibly throughthe placenta), creating a chimeric state or microchimerism. Although the number of cells decreases after delivery, microchimeric cells are known to persist for the rest of our lives[1]. This suggests that various kinds of cells including stem cell-like cells withself-renewing potential might have migrated as microchimeric cells; however, little is known about their cell type repertoire. Citation: Irie N (2011) Emerging Questions in Materno-Fetal Microchimerism. Reproductive Sys Sexual Disord S1:002. doi:10.4172/2161-038X.S1002