title: Chimeric maternal cells in offspring do not respond to renal injury, inflammatory or repair signals.
abstract: Maternal microchimerism (MMc) can persist for years in a child, and has been implicated in the pathogenesis of chronic inflammatory autoimmune diseases. Chimeric cells may either contribute to disease by acting as immune targets or expand in response to signals of injury, inflammation or repair. We investigated the role of maternal cells in tissue injury in the absence of autoimmunity by quantifying MMc by quantitative PCR in acute and chronic models of renal injury: (1) reversible acute renal injury, inflammation and regeneration induced by rhabdomyolysis and (2) chronic injury leading to fibrosis after unilateral ureteral obstruction. We found that MMc is common in the mouse kidney. In mice congenic with their mothers neither acute nor chronic renal injury with fibrosis influenced the levels or prevalence of MMc. Maternal cells expressing MHC antigens not shared by offspring (H2(b/d)) were detected at lower levels in all groups of homozygous H2(b/b) or H2(d/d) offspring, with or without renal injury, suggesting that partial tolerance to low levels of alloantigens may regulate the homeostatic levels of maternal cells within tissues. Maternal cells homozygous for H2(b) were lost in H2(b/d) offspring only after acute renal failure, suggesting that an inflammatory stimulus led to loss of tolerance to homozygous maternal cells. The study suggests that elevated MMc previously found in association with human autoimmune diseases may not be a response to non-specific injury or inflammatory signals, but rather a primary event integral to the pathogenesis of autoimmunity.
authors.affiliation: Department of Pediatrics; University of Washington; Seattle, WA USA.
authors.forename: Jesús M
authors.initials: JM
authors.lastname: López-Guisa
authors.forename: Rebecca
authors.initials: R
authors.lastname: Howsmon
authors.forename: Andrew
authors.initials: A
authors.lastname: Munro
authors.forename: Kendall M
authors.initials: KM
authors.lastname: Blair
authors.forename: Edward
authors.initials: E
authors.lastname: Fisher
authors.forename: Heidi
authors.initials: H
authors.lastname: Hermes
authors.forename: Richard
authors.initials: R
authors.lastname: Zager
authors.forename: Anne M
authors.initials: AM
authors.lastname: Stevens