Skip to content
DraconiticResearch
Search Sources API
190,839 studies31 sourcesUpdated 14 min ago
Peer-reviewedCC BYEMBO Reports

Pde1b controls cyclic nucleotide signaling in cDC1 and macrophages to regulate immune responses

  • Lais L O Rekowsky1
  • Ricardo L L da Silva1
  • Jonathan A Seenarine1
  • Ayane de Sa Resende1
  • Marissa Macchietto2
  • Tatiana R de Moura3
  • Diana M Elizondo4
  • Michael W Lipscomb1
4 affiliations
  1. 1Department of Pharmacology, University of Minnesota
  2. 2University of Minnesota Supercomputing Institute (MSCI), University of Minnesota
  3. 3Laboratory of Immunology and Molecular Biology, Federal University of Sergipe
  4. 4Department of Biological Sciences, University of Maryland Baltimore County
Read full textDOICite

Abstract

Cyclic nucleotides cAMP and cGMP are potent suppressors of immune activation, yet how their intracellular levels are regulated within antigen-presenting myeloid cells remains undefined. Here we identify phosphodiesterase 1B (Pde1b) as a lineage-restricted regulator of cyclic nucleotide signaling in conventional type 1 dendritic cells (cDC1) and a subset of macrophages. Using genetic loss-of-function models and Listeria infection, we show that Pde1b is required for immune responses. Pde1b deficiency impairs bacterial clearance and reduces antigen-specific CD8+ and CD4 + T cell expansion, while myeloid transcriptional programs are skewed towards alternative and immunoregulatory states. These defects are largely attributable to DC dysfunction, as adoptive transfer of wild-type DC in Pde1b-deficient recipients partially rescues T cell priming. Macrophages exhibit parallel defects, including reduced frequency and impaired inflammatory and antimicrobial function. Mechanistically, Pde1b loss elevates cAMP and cGMP in cDC1 and macrophages, leading to increased PKA/PKG signaling and CREB-associated transcriptional reprogramming. Pharmacological inhibition of other phosphodiesterase families does not fully recapitulate Pde1b loss. Together, these findings identify Pde1b as a cell-type-specific regulator of cyclic nucleotide signaling essential for immune responses.

Related

  1. Csx15 is a broad specificity ring nuclease bridging CRISPR-Cas and CBASS cyclic nucleotide signaling systems
    D. Klimavicius, D. Rafalski, D. Smalakyte +6
    bioRxivPreprintCC BY-NC-NDFull textMolecular biology & gene regulationbioRxiv
  2. Persistence without turnover: the RhoG G12E mutant highlights the role of nucleotide cycling in RhoG signaling
    Shah Wajed, Yann Ferrandez, Mahel Zeghouf +4
    Biochemical JournalPeer-reviewedCC BYMolecular biology & gene regulationHAL
  3. The Endogenous Negative Allosteric Modulator, Lynx1, Inhibits Nicotinic Cholinergic Signaling in the Ventral Tegmental Area to Regulate Nicotine Reinforcement
    Yasmine Sherafat, Malia Bautista, Kendyl N. Laumann +6
    The Journal of NeurosciencePeer-reviewedPublisher termsFull textMolecular biology & gene regulationPMC
  4. Immunometabolic reprogramming of macrophages by gut microbiota-derived cadaverine controls colon inflammation
    Rodrigo de Oliveira Formiga, Qing Li, Yining Zhao +26
    Cell Host & MicrobePeer-reviewedCC BY34 citedMolecular biology & gene regulationHAL
  5. Clostridium butyricum and butyrate reprogram macrophages to alleviate obesity by disrupting the LPS-EGR1 axis and its associated PI3K-Akt signaling
    Wangchang Li, Wenxin Chen, Lu Wang +10
    MicrobiomePeer-reviewedCC BY-NC-ND 4.0Molecular biology & gene regulationCrossref

Cite

BibTeXRIS
BibTeX
@article{rekowsky2026pde1b,
  title = {{Pde1b controls cyclic nucleotide signaling in cDC1 and macrophages to regulate immune responses}},
  author = {Lais L O Rekowsky and Ricardo L L da Silva and Jonathan A Seenarine and Ayane de Sa Resende and Marissa Macchietto and Tatiana R de Moura and Diana M Elizondo and Michael W Lipscomb},
  journal = {EMBO Reports},
  year = {2026},
  month = sep,
  doi = {10.1038/s44319-026-00924-z},
  url = {https://doi.org/10.1038/s44319-026-00924-z},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Pde1b controls cyclic nucleotide signaling in cDC1 and macrophages to regulate immune responses
AU  - Lais L O Rekowsky
AU  - Ricardo L L da Silva
AU  - Jonathan A Seenarine
AU  - Ayane de Sa Resende
AU  - Marissa Macchietto
AU  - Tatiana R de Moura
AU  - Diana M Elizondo
AU  - Michael W Lipscomb
PY  - 2026
DA  - 2026/09/01
JO  - EMBO Reports
DO  - 10.1038/s44319-026-00924-z
UR  - https://doi.org/10.1038/s44319-026-00924-z
AB  - Cyclic nucleotides cAMP and cGMP are potent suppressors of immune activation, yet how their intracellular levels are regulated within antigen-presenting myeloid cells remains undefined. Here we identify phosphodiesterase 1B (Pde1b) as a lineage-restricted regulator of cyclic nucleotide signaling in conventional type 1 dendritic cells (cDC1) and a subset of macrophages. Using genetic loss-of-function models and Listeria infection, we show that Pde1b is required for immune responses. Pde1b deficiency impairs bacterial clearance and reduces antigen-specific CD8+ and CD4 + T cell expansion, while myeloid transcriptional programs are skewed towards alternative and immunoregulatory states. These defects are largely attributable to DC dysfunction, as adoptive transfer of wild-type DC in Pde1b-deficient recipients partially rescues T cell priming. Macrophages exhibit parallel defects, including reduced frequency and impaired inflammatory and antimicrobial function. Mechanistically, Pde1b loss elevates cAMP and cGMP in cDC1 and macrophages, leading to increased PKA/PKG signaling and CREB-associated transcriptional reprogramming. Pharmacological inhibition of other phosphodiesterase families does not fully recapitulate Pde1b loss. Together, these findings identify Pde1b as a cell-type-specific regulator of cyclic nucleotide signaling essential for immune responses.
SN  - 1469-3178
ER  -