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Maternal retinoids control type 3 innate lymphoid cells and set the offspring immunity
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Journal Article
Maternal retinoids control type 3 innate lymphoid cells and set the offspring immunity
2014
Overview
Dietary vitamin A during pregnancy is required for the formation of secondary lymphoid organs of the developing embryo and affects the offspring’s immune competence in adulthood.
Vitamin A needed for offspring immunity
This comparison of pregnant mice on diets completely lacking vitamin A, and with low and high vitamin A content, reveals a role for maternal vitamin A metabolites — notably retinoic acid — in establishing innate immunity in the developing fetus. The vitamin is required for the formation of secondary lymphoid organs during embryonic development and affects the offspring's immune competence during adulthood.
The impact of nutritional status during fetal life on the overall health of adults has been recognized
1
; however, dietary effects on the developing immune system are largely unknown. Development of secondary lymphoid organs occurs during embryogenesis and is considered to be developmentally programmed
2
,
3
. Secondary lymphoid organ formation depends on a subset of type 3 innate lymphoid cells (ILC3) named lymphoid tissue inducer (LTi) cells
2
,
3
,
4
,
5
. Here we show that mouse fetal ILC3s are controlled by cell-autonomous retinoic acid (RA) signalling
in utero
, which pre-sets the immune fitness in adulthood. We found that embryonic lymphoid organs contain ILC progenitors that differentiate locally into mature LTi cells. Local LTi cell differentiation was controlled by maternal retinoid intake and fetal RA signalling acting in a haematopoietic cell-autonomous manner. RA controlled LTi cell maturation upstream of the transcription factor RORγt. Accordingly, enforced expression of
Rorgt
restored maturation of LTi cells with impaired RA signalling, whereas RA receptors directly regulated the
Rorgt
locus. Finally, we established that maternal levels of dietary retinoids control the size of secondary lymphoid organs and the efficiency of immune responses in the adult offspring. Our results reveal a molecular link between maternal nutrients and the formation of immune structures required for resistance to infection in the offspring.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
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/ Analysis
/ Animals
/ Cell Differentiation - drug effects
/ Cell Differentiation - immunology
/ Diet
/ Embryos
/ Female
/ Humanities and Social Sciences
/ Immunity, Innate - drug effects
/ Immunity, Innate - immunology
/ letter
/ Lymphoid Tissue - drug effects
/ Lymphoid Tissue - embryology
/ Lymphoid Tissue - immunology
/ Mice
/ Prenatal Exposure Delayed Effects - immunology
/ Receptors, Retinoic Acid - metabolism
/ Rodents
/ Science
/ Signal Transduction - drug effects
