9-cis retinoic acid modulates the type I allergic immune response

• Published in: Journal of allergy and clinical immunology Vol. 141; no. 2; pp. 650 - 658.e5
• Main Authors: Heine, Guido, MD, Hollstein, Tim, MD, Treptow, Sandra, Dipl.Ing, Radbruch, Andreas, PhD, Worm, Margitta, MD
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.02.2018; Elsevier Limited
• Subjects: 9-cis retinoic acid; Adaptive immunity; Allergies; Allergy; Allergy and Immunology; B cell; CD19 antigen; CD86 antigen; Cell activation; Cell growth; Cell migration; Cellular manufacture; Cloning; Dendritic cells; Eczema; Enzyme-linked immunosorbent assay; Flow cytometry; Hypersensitivity; IgE; Immune response; Immune response (humoral); Immunoglobulin A; Immunoglobulin E; Immunoglobulins; Interleukin 10; Lymph nodes; Lymphocytes B; Ovalbumin; Retinoic acid; Rodents; Spleen; T cell receptors; Vitamin A; Germany; Allergy; Ovalbumin; Carboxyfluorescein diacetate succinimidyl ester; 9cRA; RAR; vitamin A; 7-Aminoactinomycin D; IgE; CFSE; B-cell receptor; RXR; RA; BCR; B cell; 7-AAD; All-trans retinoic acid; Retinoic acid receptor; Retinoid X receptor; 9-cis retinoic acid; OVA; ATRA; Retinoic acid
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/j.jaci.2017.03.046

Background Vitamin A is a potent regulator of adaptive immunity. The effect of the endogenous metabolite 9-cis retinoic acid (9cRA) on allergic sensitization is unknown. Objective We sought to investigate whether and to what extent 9cRA modulates the humoral immune response. Methods BALB/c mice were sensitized and challenged with ovalbumin (OVA). 9cRA was applied repeatedly together with the antigen. Immunoglobulin production and cellular analysis were performed by using ELISA, ELISpot, and flow cytometry. Human CD19+ B cells were activated in vitro in the presence or absence of 9cRA and activation markers, and proliferation and secreted immunoglobulin levels were analyzed by using flow cytometry and ELISA. Results 9cRA applied together with repeated OVA challenge transiently increased specific serum IgA, IgE, and IgG1 serum levels (2.0- and 8.9-fold). After OVA recall, specific IgE concentrations were reduced by a mean of 57% after adding 9cRA, whereas IgA was strongly induced (20-fold), and IgG1 levels remained unchanged. Correspondingly, less specific IgE- and more IgA-secreting cells resided in the spleen in the 9cRA groups. Additionally, 9cRA promoted the migration of specific B cells to the mesenteric but not draining lymph nodes. In purified stimulated human B cells, 9cRA markedly reduced IgE production and enhanced IgA production. B-cell activation was modulated by 9cRA, reducing the expression of CD86 and promoting IL-10. Conclusions Our data indicate that 9cRA modulates the allergic immune response by reducing the IgE response but promoting the IgA response. Thus 9cRA can modulate the allergic immune response toward a non-IgE condition.