Peanut protein acts as a TH2 adjuvant by inducing RALDH2 in human antigen-presenting cells

J Allergy Clin Immunol. 2021 Jul;148(1):182-194.e4. doi: 10.1016/j.jaci.2020.11.047. Epub 2020 Dec 27.


Background: Peanut is a potent inducer of proallergenic TH2 responses in susceptible individuals. Antigen-presenting cells (APCs) including dendritic cells and monocytes instruct naive T cells to differentiate into various effector cells, determining immune responses such as allergy and tolerance.

Objective: We sought to detect peanut protein (PN)-induced changes in gene expression in human myeloid dendritic cells (mDCs) and monocytes, identify signaling receptors that mediate these changes, and assess how PN-induced genes in mDCs impact their ability to promote T-cell differentiation.

Methods: mDCs, monocytes, and naive CD4+ T cells were isolated from blood bank donors and peanut-allergic patients. APCs were incubated with PN and other stimulants, and gene expression was measured using microarray and RT quantitative PCR. To assess T-cell differentiation, mDCs were cocultured with naive TH cells.

Results: PN induced a unique gene expression profile in mDCs, including the gene that encodes retinaldehyde dehydrogenase 2 (RALDH2), a rate-limiting enzyme in the retinoic acid (RA)-producing pathway. Stimulation of mDCs with PN also induced a 7-fold increase in the enzymatic activity of RALDH2. Blocking antibodies against Toll-like receptor (TLR)1/TLR2, as well as small interfering RNA targeting TLR1/TLR2, reduced the expression of RALDH2 in PN-stimulated APCs by 70%. Naive TH cells cocultured with PN-stimulated mDCs showed an RA-dependent 4-fold increase in production of IL-5 and expression of integrin α4β7.

Conclusions: PN induces RALDH2 in human APCs by signaling through the TLR1/TLR2 heterodimer. This leads to production of RA, which acts on TH cells to induce IL-5 and gut-homing integrin. RALDH2 induction by PN in APCs and RA-promoted TH2 differentiation could be an important factor determining allergic responses to peanut.

Keywords: IL-5; Peanut allergy; RALDH2; T(H)2; TLR2; dendritic cells; integrin α(4)β(7); monocytes; peanut; retinoic acid.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aldehyde Dehydrogenase 1 Family / immunology*
  • Antigen-Presenting Cells / immunology*
  • Arachis / immunology*
  • CD4-Positive T-Lymphocytes / immunology
  • Cell Differentiation / immunology
  • Cells, Cultured
  • Dendritic Cells / immunology
  • HEK293 Cells
  • Humans
  • Hypersensitivity / immunology
  • Lymphocyte Activation / immunology
  • Monocytes / immunology
  • Retinal Dehydrogenase / immunology*
  • Th2 Cells / immunology*
  • Tretinoin / immunology


  • Tretinoin
  • Aldehyde Dehydrogenase 1 Family
  • ALDH1A2 protein, human
  • Retinal Dehydrogenase