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AOP: 618
Title
PPARgamma activation leads to a diminished vaccine response
Short name
Graphical Representation
Point of Contact
Contributors
- Léo SPORTES-MILOT
- Etienne Blanc
Coaches
OECD Information Table
| OECD Project # | OECD Status | Reviewer's Reports | Journal-format Article | OECD iLibrary Published Version |
|---|---|---|---|---|
This AOP was last modified on January 16, 2026 11:46
Revision dates for related pages
| Page | Revision Date/Time |
|---|---|
| Inhibition, Nuclear factor kappa B (NF-kB) | March 02, 2023 01:58 |
| Diminished survival of naive B lymphocytes | December 03, 2025 12:04 |
| Diminished proliferation of activated B lymphocytes | December 03, 2025 12:06 |
| Diminished differentiation of activated B lymphocytes | December 03, 2025 12:07 |
| Diminished vaccine response | December 03, 2025 12:08 |
| Reduced antibody production | December 03, 2025 12:10 |
| Activation of specific nuclear receptors, PPAR-gamma activation | September 16, 2017 10:17 |
| Inhibition, Nuclear factor kappa B (NF-kB) leads to Lower survival B lymphocytes | December 03, 2025 12:10 |
| Inhibition, Nuclear factor kappa B (NF-kB) leads to Diminished proliferation of activated B lymphocytes | December 03, 2025 12:11 |
| Inhibition, Nuclear factor kappa B (NF-kB) leads to Diminished differentiation of activated B lymphocytes | December 03, 2025 12:11 |
| Diminished differentiation of activated B lymphocytes leads to Reduced antibody production | December 03, 2025 12:11 |
| Reduced antibody production leads to Diminished vaccine response | December 03, 2025 12:11 |
| Lower survival B lymphocytes leads to Diminished proliferation of activated B lymphocytes | December 03, 2025 12:11 |
| Diminished proliferation of activated B lymphocytes leads to Diminished differentiation of activated B lymphocytes | December 03, 2025 12:12 |
| Activation of specific nuclear receptors, PPAR-gamma activation leads to Inhibition, Nuclear factor kappa B (NF-kB) | January 16, 2026 11:46 |
Abstract
Activation of peroxisome proliferator-activated receptor gamma (PPARγ) by exogenous ligands, such as environmental pollutants including certain PFAS, or endogenous ligands produced by cellular metabolism, is now recognized as a factor in modulating the immune response. The TDI of 4.4 ng/kg/bw (for PFAS) has been established based on its immunotoxic effect. However, the mechanistic understanding of the action of PFAS on the immune system has not really been studied in the literature. This is especially relevant, given evidence from cohort studies showing that PFAS exposure correlates with weaker responses to childhood vaccines, such as diphtheria and tetanus, raising public health implications for vaccination programs in contaminated areas.
In this AOP proposal, we choose the MIE PPARγ activation. It induces the expression of genes involved in anti-inflammatory pathways, including the inhibition of NF-κB signaling in B lymphocytes, a crucial subset of cells, particularly for the adaptive immune response.
Thus, constructing an Adverse Outcome Pathway (AOP) linking PPARγ activation to diminished vaccine response via NF-κB inhibition in B cells highlights the importance of interactions between environmental factors, B lymphocyte regulation, and adaptive immunity, a novel aspect that remains underexplored in AOPwiki.
AOP Development Strategy
Context
Strategy
Summary of the AOP
Events:
Molecular Initiating Events (MIE)
Key Events (KE)
Adverse Outcomes (AO)
| Type | Event ID | Title | Short name |
|---|
| MIE | 1028 | Activation of specific nuclear receptors, PPAR-gamma activation | Activation of specific nuclear receptors, PPAR-gamma activation |
| KE | 202 | Inhibition, Nuclear factor kappa B (NF-kB) | Inhibition, Nuclear factor kappa B (NF-kB) |
| KE | 2394 | Diminished survival of naive B lymphocytes | Lower survival B lymphocytes |
| KE | 2395 | Diminished proliferation of activated B lymphocytes | Diminished proliferation of activated B lymphocytes |
| KE | 2396 | Diminished differentiation of activated B lymphocytes | Diminished differentiation of activated B lymphocytes |
| KE | 2398 | Reduced antibody production | Reduced antibody production |
| AO | 2397 | Diminished vaccine response | Diminished vaccine response |
Relationships Between Two Key Events (Including MIEs and AOs)
| Title | Adjacency | Evidence | Quantitative Understanding |
|---|
Network View
Prototypical Stressors
Life Stage Applicability
Taxonomic Applicability
Sex Applicability
Overall Assessment of the AOP
Domain of Applicability
Essentiality of the Key Events
Evidence Assessment
Known Modulating Factors
| Modulating Factor (MF) | Influence or Outcome | KER(s) involved |
|---|---|---|