Vitamin A controls the allergic response through T follicular helper cell as well as plasmablast differentiation. Issue 4 (20th September 2020)

• Record Type: Journal Article
• Authors: Scholz, Josephine; Kuhrau, Julia; Heinrich, Frederik; Heinz, Gitta Anne; Hutloff, Andreas; Worm, Margitta; Heine, Guido
• Is Part Of: Allergy. Volume 76:Issue 4(2021)
• Page Start: 1109
• Page End: 1122
• Publication Date: 2020-09-20
• Subjects: 9‐cis retinoic acid -- allergy -- RAR -- Tfh cells -- vitamin A; Allergy -- Periodicals; 616.97
• DOI: 10.1111/all.14581
• Languages: English
• ISSNs: 0105-4538

Abstract

Abstract: Background: Vitamin A regulates the adaptive immune response and a modulatory impact on type I allergy is discussed. The cellular mechanisms are largely unknown. Objective: To determine the vitamin A‐responding specific lymphocyte reaction in vivo. Methods: Antigen‐specific B and T lymphocytes were analyzed in an adoptive transfer airway inflammation mouse model in response to 9‐cis retinoic acid (9cRA) and after lymphocyte‐specific genetic targeting of the receptor RARα. Flow cytometry, quantitative PCR, next‐generation sequencing, and specific Ig‐ELISA were used to characterize the cells functionally. Results: Systemic 9cRA profoundly enhanced the specific IgA‐secreting B‐cell frequencies in the lung tissue and serum IgA while reducing serum IgE concentrations. RARα overexpression in antigen‐specific B cells promoted differentiation into plasmablasts at the expense of germinal center B cells. In antigen‐specific T cells, RARα strongly promoted the differentiation of T follicular helper cells followed by an enhanced germinal center response. Conclusions: 9cRA signaling via RARα impacts the allergen‐specific immunoglobulin response directly by the differentiation of B cells and indirectly by promoting T follicular helper cells. Abstract : This study analyzes antigen‐specific B and T lymphocytes in an adoptive transfer airway inflammation mouse model in response to 9‐cis retinoic acid (9cRA) and after lymphocyte‐specific genetic targeting of the receptor RARα. RARα overexpression in antigen‐specific B cells promotes differentiation into plasmablasts at the expense of germinal center B cells. In antigen‐specific T cells, RARα strongly promotes the differentiation of T follicular helper cells followed by an enhanced germinal center response. Abbreviations: FDC, follicular dendritic cell; GC, germinal center; RARα, retinoic acid receptor alpha; Tfh, T follicular helper cell.