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Microchimerism and Skin Disease: True-True Unrelated?

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Microchimerism and Skin Disease: True-True Unrelated? View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector See related article on pg 345 COMMENTARY cells that can form cells of all lineages: Microchimerism and Skin Disease: ectodermal, mesenchymal and endo- dermal (Grove et al., 2004). True-True Unrelated? Many studies support the concept of Anita C. Gilliam1 transdifferentiation — the reprogram- ming of stem cells to differentiate into Microchimerism, the stable presence of foreign cells in an individual, may result multiple different cell types appropri- from trafficking during pregnancy or from organ or hematopoietic transplan- ate to their local environments (Alonso tation, and has been hypothesized to cause autoimmunity and certain skin and Fuchs, 2003). Thus the mater- diseases. Yet microchimeric cells are found in normal individuals and may be nal–fetal exchange via the placenta, important to tissue repair. Thus microchimerism may be common, and find- coupled with the enormous potential ing microchimeric cells in diseased as well as normal tissue may be a “true-true of stem cells to produce a variety of unrelated” situation. cell types, might produce a microchi- Journal of Investigative Dermatology (2006) 126, 239–241. doi:10.1038/sj.jid.5700061 merism of not only hematopoietic cells but also cells of all possible lineages, including skin cells. Microchimerism and Cell Trafficking ferentiated cells such as fetal nucleated During Pregnancy erythrocytes or placental trophoblasts Microchimerism and Transplantation The word ‘chimera’ comes from a in maternal blood are a useful marker The study of microchimerism in trans- mythological animal that is a com- of placental health. When an increased plantation biology allows manipula- bination of lion, goat and snake. In number of nucleated erythrocytes and tion of the variables and has led to modern biology, ‘microchimerism’ is trophoblasts are present in maternal some remarkable findings. Recipients the stable presence of low numbers circulation, abnormal placental bar- of transplanted hematopoietic cells of foreign cells in an individual. For rier function such as in preeclampsia remain chimeric for donor and recipi- instance, approximately 8% of identi- or fetal aneuploidy can also be present ent immune cells for a long time after cal twins are chimeric for each other’s (Bianchi, 2000). These differentiated transplantation. Because bone mar- leukocytes because of a shared blood cells do not survive long in maternal row stem cells are diverse and plastic, supply in utero. In single pregnancies, circulation. However, fetal stem and other tissues also become chimeric for the placenta allows passage of mater- progenitor cells can proliferate, differ- donor and recipient after bone marrow nal and fetal cells in both directions, entiate and travel to various maternal transplantation. Bone marrow-derived which explains how fetal and maternal tissues. Cord blood is an important cells can contribute to tissue repair microchimerism can occur after preg- source of fetal stem cells, which are (skeletal muscle, cardiac muscle, liver, nancy. Cord blood samples collected known to have a mobile and plastic lung, kidney, central nervous system). for transplantation contain up to 20% phenotype, and it is the likely source of Bone marrow-derived Y chromosome- maternal cells by in situ hybridiza- cells in maternal microchimerism. Fetal positive keratin-positive cells can be tion and up to 40% maternal cells by hematopoietic stem cells, and presum- found in skin of female recipients of PCR (Lo et al., 1996). These foreign ably their progeny T and B lympho- bone marrow transplanted from male cells can persist in both mother and cytes, monocytes and NK cells, have donors (Grove et al., 2004). child, giving rise to microchimerism. been demonstrated in maternal circula- Microchimerism also occurs in recip- Bianchi et al. reported that CD34+ and tion and tissue. Similarly, maternal stem ients of solid organ transplants (lung, CD34+CD38+ fetal cells were present cells can survive and proliferate in the liver and kidney). Starzl and colleagues in maternal circulation up to 27 years tissues of offspring because of the two- proposed that organ engraftment is a after pregnancy (Bianchi et al., 1996). way traffic of cells via the placenta. form of partial tolerance that is depen- This microchimerism is more likely dent on leukocyte chimerism generated when the fetus is HLA compatible Stem Cells by ‘passenger leukocytes’ and stem with the mother. Fetal microchimerism Multiple types of stem cells have been cells in solid organ grafts (Starzl, 2004). is not as well characterized but is an identified, and the list of stem cells in In these situations, the microchimerism intriguing new area of investigation. adult individuals continues to expand. studied is of leukocytes, transmitted What types of cells are seen in Adult bone marrow contains hemato- to the recipient via transplantation of microchimerism due to maternal–fetal poietic stem cells, mesenchymal stem passenger leukocytes in a solid organ exchange via the placenta? Highly dif- cells and multipotent adult progenitor such as intestine, lung, liver or kid- ney. Anderson and Matzinger studied 1Department of Dermatology, Case/University Hospitals of Cleveland, Cleveland, Ohio, USA microchimerism produced by passen- Correspondence: Dr. Anita C. Gilliam, Department of Dermatology, Case/University Hospitals of ger leukocytes in skin grafts in mice and Cleveland, 11100 Euclid Ave, Cleveland, Ohio 44106-5028, USA. Email: [email protected] found that the outcomes varied depend- © 2006 The Society for Investigative Dermatology www.jidonline.org 239 COMMENTARY ing mainly on the recipients’ immuno- to conflicting data. For instance, other A new paradigm — the presence of logical maturity and on the antigenic autoimmune diseases with female pre- cells other than leukocytes in micro- differences. They concluded that donor dominance and a later onset do not chimerism as a possible factor in skin cells could be either tolerogenic or have demonstrable microchimerism disease — is explored in the article immunogenic, depending on the condi- (Sjögren syndrome, primary biliary by Khosrotehrani et al. in this issue tions (Anderson and Matzinger, 2001). cirrhosis). Also, microchimerism can (2006). The authors identified mater- Therefore, the rules for the sequelae of be shown in normal individuals and nally derived cytokeratin-positive cells microchimerism due to transplantation in non-autoimmune diseases such as in archival paraffin-embedded sections in humans are complex and are still infectious hepatitis and cervical can- of the skin of 11 of 12 male children being defined. cer (Johnson and Bianchi, 2004). A with pityriasis lichenoides by fluores- case control study of individuals with cent in situ hybridization with X and Microchimerism and Autoimmunity a variety of connective tissue diseases Y chromosome-specific probes. These What are the consequences of micro- led to the conclusion that microchime- maternally derived cells were also chimerism? It has been proposed that rism was common in all individuals, present in biopsies of skin from male microchimerism may lead to auto- including normal ones (Gannage et control subjects without skin disease, immune disease in some individuals al., 2002). Bianchi, who first reported but with a lower frequency (4 of 7) and with a permissive genetic makeup. microchimerism in humans, concludes density (approximately 20-fold lower Autoimmune diseases in recipients that multiple factors may determine in pityriasis lichenoides patients than of transplanted hematopoietic cells whether microchimerism is a cause of in normal subjects). are well known. These include graft- disease: presence of foreign cells not The search for foreign cells in skin versus-host disease, which can only in blood but also in diseased tis- disorders has produced conflicting be lupus-like or scleroderma-like, sue; tissue type; disease type; history data. Inherent in these experiments are Sjögren’s syndrome, primary biliary of pregnancy; and immune status are the technical difficulties of fluorescent cirrhosis, myositis, myasthenia gravis, all important (Johnson and Bianchi, in situ hybridization or PCR analysis in hyper- and hypothyroidism and auto- 2004). To date, the connection between archived specimens. Background can immune cytopenias (thrombocytope- microchimerism and disease has not be high and interpretation difficult. nia, leukopenia, neutropenia). Disease yet been definitively made. In fact, it Often the sequences of interest are in transplant recipients resembles that has also been suggested that fetal cells also found in normal control subjects. in individuals with the correspond- may provide a renewable source of For instance, women with lichen scle- ing primary autoimmune diseases. stem cells that can help with repair of rosis with and without squamous-cell The dysregulation of tolerance in the maternal tissues, a positive rather than carcinoma, vulvar Paget’s disease, and transplant recipient is thought to allow a negative outcome of microchime- normal vulvar skin who had male child- development of autoreactive T-cell rism. One hypothesis is that stem cells ren were no different when Y chromo- clones, leading to autoimmune dis- may migrate to sites of inflammation some sequences were evaluated by ease. Whether this results from micro- and differentiate into cells that partici- PCR in paraffin-embedded sections. chimerism or
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