Food allergies impact millions globally, and flavonoids have emerged as potential natural solutions to help balance the immune response and reduce inflammation linked to these allergies. A recent study has revealed that kaempferol, a type of flavonoid, showcases anti-inflammatory properties by facilitating the development of regulatory T-cells. This effect is achieved through enhanced RADLH2 expression in dendritic cells, mediated by AhR and PU.1/IRF-4-dependent pathways. Furthermore, kaempferol was found to lessen various allergic reactions in mice suffering from food allergies.
The prevalence of allergic conditions like asthma, atopic dermatitis, and food allergies has been rising in recent years. Food allergies, which can include reactions to items like milk, peanuts, eggs, and shellfish, are particularly widespread, affecting millions globally. These allergies typically arise when the immune system overreacts to innocuous substances found in food and the environment. Flavonoids, compounds found in numerous fruits and vegetables, are recognized for their anti-allergic properties and hold promise as natural treatments for allergies.
To delve deeper into potential treatments for these allergies, it’s worth exploring a fascinating mechanism that helps combat allergic reactions in our bodies. In the intestines, unique dendritic cells (DCs) generate an enzyme known as RALDH2 (retinaldehyde dehydrogenase 2), which transforms retinal, a substance derived from vitamin A, into retinoic acid. This retinoic acid then encourages the formation of regulatory T-cells, a type of immune cell that helps dampen the immune response associated with allergies.
RALDH2 clearly plays a crucial role in addressing food allergies. However, can certain flavonoids boost RALDH2 levels in DCs?
This question was tackled by a research team led by Professor Chiharu Nishiyama from the Tokyo University of Science (TUS), with their findings published online in Allergy on December 11, 2024. The researchers screened approximately 40 different flavonoids to assess their impact on RALDH2 levels in DCs, identifying kaempferol as the most effective, prompting them to investigate it further. Key contributors to this study included Ms. Miki Takahashi, a 2023 TUS graduate, Dr. Kazuki Nagata, Assistant Professor at TUS, and Ms. Yumi Watanuki, a 2019 TUS graduate.
Kaempferol is present in several foods, including kale, beans, tea, spinach, and broccoli, and is one of the most thoroughly researched flavonoids due to its positive effects on human health. The researchers noted that treatment with kaempferol boosted RALDH2 expression and functionality in DCs. Moreover, these kaempferol-treated DCs facilitated the growth of regulatory T-cells, highlighting its role in modulating the immune response.
To comprehend the specific mechanisms at play, they concentrated on a receptor known as the aryl hydrocarbon receptor (AhR), which is influenced by kaempferol. Their investigations indicated that kaempferol acts as an ‘antagonist’ to AhR, thereby enhancing the development of regulatory T-cells. The next phase involved examining elements that influence the Aldh1a2 gene, responsible for producing Radlh2.
“Previously, we reported that PU.1 and IRF-4 were fundamental molecules in regulating the Aldh1a2 gene in dendritic cells,” explains Prof. Nishiyama. “In this study, we discovered that the expression and functionality of PU.1 and IRF-4 were heightened in dendritic cells stimulated with kaempferol,” further unpacking the PU.1/IRF-4-dependent mechanism by which kaempferol exerts its anti-inflammatory influence.
To evaluate kaempferol’s impact on immune responses in live organisms, the researchers induced allergies in mice using OVA (ovalbumin) from egg whites. They observed that kaempferol administration mitigated allergic symptoms in these mice. “The swift drop in body temperature and the allergic diarrhea observed post-OVA administration were notably reduced in mice receiving kaempferol,” reports Prof. Nishiyama.
These findings position kaempferol as a highly promising natural approach for treating food allergies. Nonetheless, the authors emphasize the need for further research, particularly involving human cells, to replicate these results and consider kaempferol in allergy treatment. While this study honed in on kaempferol’s ability to reduce inflammation, flavonoids in general represent promising compounds for alleviating allergies, as they are found in a diverse range of foods.
The authors propose that the structural features of flavonoids might enhance their capacity to stimulate regulatory T-cell development. This revelation could significantly change our approach to allergy treatment, as consuming foods rich in flavonoids may provide natural relief from allergic reactions.
Reinforcing the necessity of including flavonoid-rich foods in your daily diet, Prof. Nishiyama states, “Regular consumption is anticipated to diminish allergies, inflammation, and autoimmune diseases that arise or worsen due to an overstimulated immune response.”
