Selective organ specific inflammation in offspring harbouring microchimerism from strongly alloreactive mothers

Leveque, Lucie, Hodgson, Samantha, Peyton, Stephen, Koyama, Motoko, Macdonald, Kelli P. A. and Khosrotehrani, Kiarash (2013) Selective organ specific inflammation in offspring harbouring microchimerism from strongly alloreactive mothers. Journal of Autoimmunity, 50 51-58. doi:10.1016/j.jaut.2013.10.005

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Author Leveque, Lucie
Hodgson, Samantha
Peyton, Stephen
Koyama, Motoko
Macdonald, Kelli P. A.
Khosrotehrani, Kiarash
Title Selective organ specific inflammation in offspring harbouring microchimerism from strongly alloreactive mothers
Journal name Journal of Autoimmunity   Check publisher's open access policy
ISSN 0896-8411
1095-9157
Publication date 2013-11-20
Sub-type Article (original research)
DOI 10.1016/j.jaut.2013.10.005
Open Access Status
Volume 50
Start page 51
End page 58
Total pages 8
Place of publication Camden, London, United Kingdom
Publisher Academic Press
Language eng
Formatted abstract
Highlights
• Presence and persistence of maternal microchimeric cells throughout life.
• Offspring from alloreactive or immunodeficient mothers have different outcomes.
• Increased frequency of gut inflammation in offspring of alloreactive mothers.
• Alloreactive maternal cells changed offspring's regulatory T cells development.
• Maternal alloreactivity during foetal period predisposes to offspring auto-immunity.

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.
Keyword Maternal microchimerism
Pregnancy
Regulatory T cells
Autoimmunity
Self-antigens
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Available online 20 November 2013

Document type: Journal Article
Sub-type: Article (original research)
Collections: UQ Centre for Clinical Research Publications
Official 2014 Collection
School of Medicine Publications
 
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Citation counts: TR Web of Science Citation Count  Cited 6 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 7 times in Scopus Article | Citations
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Created: Wed, 11 Dec 2013, 00:23:37 EST by Roheen Gill on behalf of UQ Centre for Clinical Research