All-Trans Retinoic Acid Enhances Antibody Production by Inducing the Expression of Thymic Stromal Lymphopoietin Protein

Abstract

Many classical vaccines contain whole pathogens and, thus, may occasionally induce adverse effects, such as inflammation. Vaccines containing purified rAgs resolved this problem, but, owing to their low antigenicity, they require adjuvants. Recently, the use of several cytokines, including thymic stromal lymphopoietin (TSLP), has been proposed for this purpose. However, it is difficult to use cytokines as vaccine adjuvants in clinical practice. In this study, we examined the effects of all- retinoic acid (atRA) on TSLP production and Ag-induced Ab production. Application of atRA onto the ear lobes of mice selectively induced TSLP production without inducing apparent inflammation. The effects appeared to be regulated via retinoic acid receptors γ and α. Treatment with atRA was observed to enhance OVA-induced specific Ab production; however, this effect was completely absent in TSLP receptor-knockout mice. An enhancement in Ab production was also observed when recombinant hemagglutinin was used as the Ag. In conclusion, atRA was an effective adjuvant through induction of TSLP production. Therefore, we propose that TSLP-inducing low m.w. compounds, such as atRA, may serve as effective adjuvants for next-generation vaccines.

Hypoxia inhibits TNF-α-induced TSLP expression in keratinocytes

“…Both transcription factors NF-κB and AP-1 regulate the expression of human TSLP protein [6]. In addition, nuclear receptors, which include vitamin D [7] and retinoic acid receptors [8] also increased TSLP expression in mice.…”

Enzymatically synthesized exopolysaccharide of a probiotic strain Leuconostoc mesenteroides NTM048 shows adjuvant activity to promote IgA antibody responses

“…Using murine bone marrowderived dendritic cells, we previously reported that NTM048 EPS increased the gene expression levels of IL-6, which plays a crucial role in the differentiation of IgA B cells, [24][25][26] and RALDH2, which catalyzes retinal to form retinoic acid and stimulates antigen-specific antibody production through thymic stromal lymphopoietin. 26,52 Furthermore, in this study, we could obtain a suggestion that the enhanced interaction by α-1,3-glucan between Gtf2-S-glucan and dendritic cells might induce stronger adjuvanticity than NTM048 EPS (Figure 9).…”

The Protective HIV-1 Envelope gp41 Antigen P1 Acts as a Mucosal Adjuvant Stimulating the Innate Immunity

“…The P1-induced TSLP secretion by nasal epithelial cell shown here could thus constitute the initial adjuvant activity achieved by P1 used in a nasal vaccine formulation. TSLP offers several advantages for stimulation of the local immunity and induction of specific antibody production, two main goals of mucosal vaccination ( 18 ). In particular, TSLP affects polarization towards Th2 immune responses, promotion of IgA class switching, and mediates the generation and maintenance of memory T cells ( 48 ).…”

“…TSLP induced a strong humoral response both in serum and at the genital level following intranasal immunization, comparable to the adjuvant effect of cholera toxin (CT) tested in parallel. In addition, a new study reported that all-trans retinoic acid (RA) shows adjuvant activity through TSLP production ( 18 ). Furthermore, a recent study showed that TSLP and TSLP-receptor (TSLP-R) were up-regulated in mucosal DCs of mice nasally immunized with pneumococcal surface protein A plus CT ( 19 ) and that in TSLP-R knockout mice, the specific IgA response is remarkably reduced.…”