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Development and Functional Characterization of Murine Tolerogenic Dendritic Cells
Published on: May 18, 2018
The Programming Effect of Plant-Based DHA, Along with Equivalent AA, on Immune System and Oral Tolerance Development
Dhruvesh Patel1, Jaqueline Munhoz1, Susan Goruk1
1Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, Alberta, Canada.
Insights
Early life supplementation with docosahexaenoic acid (DHA) and arachidonic acid (AA) may promote oral tolerance (OT) in allergy-prone infants. This study found that DHA and AA supplementation promoted T helper type-1 immune responses, potentially influencing OT development.
Area of Science:
- Immunology
- Nutrition Science
- Pediatrics
Background:
- The impact of docosahexaenoic acid (DHA) and arachidonic acid (AA) on oral tolerance (OT) development in infants prone to allergies is not well understood.
- Early life nutrition plays a crucial role in immune system development and the establishment of tolerance.
Purpose of the Study:
- To investigate the effects of early life supplementation with DHA and AA on the development of oral tolerance to ovalbumin (ova) in allergy-prone mice.
- To assess how DHA and AA, administered during the suckling and weaning periods, influence immune responses related to tolerance.
Main Methods:
- Allergy-prone BALB/c mouse pups were exposed to diets supplemented with DHA and AA or control diets during the suckling and weaning periods.
- Oral tolerance was induced by daily oral administration of ovalbumin (ova) or placebo between 21-25 days.
- Immune responses, including immunoglobulin levels and splenocyte cytokine production, were analyzed at 6 weeks of age.
Main Results:
- DHA and AA supplementation during the suckling period was associated with significantly lower plasma concentrations of ova-specific IgE.
- Oral ovalbumin administration induced OT, characterized by suppressed splenocyte production of IgG, IgG1, IL-2, and IL-6.
- DHA+AA supplementation influenced cytokine profiles, promoting T helper type-1 responses (IL-2, IFNγ, IL-1β) and reducing T helper type-2 cytokines (IL-4, IL-6) upon ova stimulation.
Conclusions:
- Early life DHA and AA supplementation may positively influence oral tolerance development in allergy-prone offspring.
- These fatty acids appear to promote a shift towards T helper type-1 immune responses, which could be beneficial for establishing tolerance and preventing allergies.
Background:
Docosahexaenoic acid (DHA) and arachidonic acid (AA) on oral tolerance (OT) development in allergy-prone infants is less known.
Objectives:
We aim to determine the effects of early life DHA supplementation (1% of total fat, from novel canola oil), along with AA, on OT toward ovalbumin (ova, egg protein) in allergy-prone BALB/c pups at 6-wk.
Methods:
Breastfeeding dams (n ≥ 10/diet) were fed DHA+AA (1% DHA, 1% AA wt/wt of total fat) or control (0% DHA, 0% AA) suckling period diet (SPD) during which pups consumed dam's milk. At 3-wk, pups from each SPD group were assigned to either the control or DHA+AA weaning diet. For OT, pups from each diet group were either orally fed ova or placebo daily from 21-25 d. Systemic immunization to ova was induced through intraperitoneal injections before euthanizing 6-wk pups. Ova-specific immunoglobulin (ova-Ig) and splenocytes ex-vivo cytokine response to different stimuli were analyzed using a 3-factor analysis of variance.
Results:
OT-induced suppression was seen in ova-stimulated splenocyte ex-vivo response, where ova-tolerized pups showed significantly lower total immunoglobulin (Ig)G, IgG1, interleukin (IL)-2 and IL-6 production than sucrose (placebo) pups. DHA+AA SPD was associated with 3 times lower plasma concentrations of ova-IgE (P = 0.03) than controls. DHA+AA weaning diet resulted in lower T helper type-2 cytokines (IL-4 and IL-6) with ova stimulation than controls, which may benefit OT. DHA+AA SPD resulted in significantly higher T cell cytokine response [IL-2, interferon-gamma, (IFNγ) and IL-1β] to anti-CD3/CD28 stimulation than controls. The splenocytes stimulated with lipopolysaccharide produced lower inflammatory cytokines (IFNγ, tumor necrosis factor-alpha, IL-6, and C-X-C motif ligand 1), which may be because of lower CD11b+CD68+ splenocytes proportion in pups from DHA+AA SPD than control (all P < 0.05).
Conclusions:
DHA and AA in early life may influence OT in allergy-prone BALB/c mouse offspring, as they effectively promote T helper type-1 immune responses.

