title: Selective organ specific inflammation in offspring harbouring microchimerism from strongly alloreactive mothers.
abstract: The origins of autoimmunity are not yet understood despite significant advances in immunology. The trafficking of maternal cells to the offspring represents the very first immunological event in foetal life and is reinforced during lactation. The persistence of maternal cells in offspring's tissues and circulation has been associated with several autoimmune disorders. However a direct causal effect has never been demonstrated. Maternal T cells specifically targeting foetal insulin producing cells have been shown to generate islet inflammation without directly participating in this process. Our objective was to evaluate if alloreactive maternal cells could directly trigger a graft-versus host like reaction or indirectly influence the development of the offspring's regulatory T cells favouring autoimmunity. We adopted a breeding strategy comparing genetically identical offspring from either strongly alloreactive transgenic mothers compared to immunodeficient mothers. We detected maternal alloreactive T cells in the offspring and early signs of inflammation in small intestine of 6 weeks old offspring. Interestingly, CD4(+) Foxp3(+) regulatory T cell frequency was diminished in mesenteric lymph nodes from eight months old offspring born of alloreactive mothers compared to offspring of immunodeficient mothers. Our study favours a hypothesis where highly alloreactive maternal cell microchimerism indirectly predisposes offspring to autoimmunity.
authors.affiliation: The University of Queensland, UQ Centre for Clinical Research, Experimental Dermatology Group, Brisbane, Australia; QIMR Berghofer Medical Research Institute, Brisbane, Australia. Electronic address: lucie.leveque@uq.edu.au.
authors.forename: Lucie
authors.initials: L
authors.lastname: Leveque
authors.affiliation: The University of Queensland, UQ Centre for Clinical Research, Experimental Dermatology Group, Brisbane, Australia.
authors.forename: Samantha
authors.initials: S
authors.lastname: Hodgson
authors.affiliation: Pathology Queensland, Royal Brisbane Hospital, Brisbane, Australia.
authors.forename: Stephen
authors.initials: S
authors.lastname: Peyton
authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, Australia.
authors.forename: Motoko
authors.initials: M
authors.lastname: Koyama
authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, Australia.
authors.forename: Kelli P A
authors.initials: KP
authors.lastname: MacDonald
authors.affiliation: The University of Queensland, UQ Centre for Clinical Research, Experimental Dermatology Group, Brisbane, Australia.
authors.forename: Kiarash
authors.initials: K
authors.lastname: Khosrotehrani
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000235:genetics / Q000276:immunology*; D015551:Autoimmunity; D046528:Chimerism; D003433:Crosses, Genetic; D005260:Female; D005333:Fetus; D015870:Gene Expression; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000473:pathology; D050417:Insulin-Secreting Cells / Q000276:immunology* / Q000473:pathology; D007421:Intestine, Small / Q000276:immunology* / Q000473:pathology; D008297:Male; D008431:Maternal-Fetal Exchange / Q000276:immunology; D051379:Mice; D009035:Mothers; D011247:Pregnancy; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000473:pathology
chemical_list: D001324:Autoantigens
keywords: Autoimmunity; Maternal microchimerism; Pregnancy; Regulatory T cells; Self-antigens