The Effects of All-Trans Retinoic Acid on the Induction of Oral Tolerance in a Murine Model of Bronchial Asthma

Abstract

Background: Active suppression induced by regulatory T (Treg) cells is reported to be one of the mechanisms involved in oral tolerance. All-trans retinoic acid (ATRA) has been reported to affect Treg cell differentiation. The present study examined the effects of ATRA on the induction of oral tolerance in a murine model of bronchial asthma. Methods: BALB/c mice were sensitized to and challenged with ovalbumin (OVA) through feeding followed by OVA challenges. In some study groups ATRA was orally administered concomitantly with OVA feeding either in the presence or absence of the retinoic acid receptor antagonist LE135. Lung CD4⁺ T cells were isolated from mice exposed to ATRA and/or OVA, and transferred to control mice. Airway hyperresponsiveness (AHR), cell counts and cytokine levels in bronchoalveolar lavage (BAL) fluid, and lung histology were assessed. Results: Concomitant administration of ATRA with OVA ameliorated AHR, airway eosinophilia, elevation of cytokines in BAL fluid and goblet cell metaplasia. The proportion of Treg cells in the lungs was increased in mice treated with OVA and ATRA, as compared to those treated with OVA only. Transfer of lung CD4⁺ T cells from mice treated with OVA and ATRA induced suppression of AHR and airway inflammation. LE135 completely reversed the effects of ATRA on AHR, airway allergic inflammation and the number of Treg cells in the lungs. Conclusion: These data suggested that oral administration of ATRA with OVA had the potential to enhance oral tolerance in this murine model of bronchial asthma. These effects were mediated, at least in part, by Treg cell expansion.

Impact of Retinoic Acid on Immune Cells and Inflammatory Diseases

“…The administration of RA may attenuate inflammation by increasing the population of regulatory T cells in the lung and decreasing the tissue damage caused by inflammation [ 18 , 19 ]. The association between RA and ovalbumin in oral tolerance in a murine model of bronchial asthma efficiently inhibited the inflammatory response and decreased eosinophilic infiltration besides Treg cells induction in the lung [ 132 ]. Treatment with atRA was able to attenuate airway inflammation by inhibiting Th2 and Th17 cytokines and downregulating the expression of the GATA3 and ROR γ t transcription factors in the lung [ 128 ].…”

Mega doses of retinol: A possible immunomodulation in Covid‐19 illness in resource‐limited settings

“…Importantly, there is increased asthma incidence in children with deficiency of vitamin A and lower retinoid concentrations correlated with severe asthma 67,68 . In murine model of ovalbumin‐induced pulmonary inflammation, RA administration led to induction of Tregs in the lung besides decreased eosinophilic infiltration 69 . ATRA downregulated Th2 and Th17 cells by inhibiting GATA3 and RORγt in the lung 70 .…”

Dietary Glucose Consumption Promotes RALDH Activity in Small Intestinal CD103+CD11b+ Dendritic Cells

“…Dietary supplementation of RA in the context of cutaneous T cell lymphoma and acute promyelocytic leukemia, have been shown to have beneficial outcome (68)(69)(70)(71). Furthermore, many studies highlight anti-inflammatory activities of RA at mucosal sites and tissues, such as intestinal mucosa, airways, lung, central nervous system and skin (72)(73)(74)(75)(76)(77)(78)(79)(80)(81)(82). In addition to the effect of RA on cancer and inflammatory diseases, vitamin A or its metabolites play an important role to suppress diet-induced obesity and insulin resistance (83)(84)(85).…”