PMID- 37765223
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20231003
IS  - 1999-4923 (Print)
IS  - 1999-4923 (Electronic)
IS  - 1999-4923 (Linking)
VI  - 15
IP  - 9
DP  - 2023 Aug 31
TI  - Modulation of Human Dendritic Cell Functions by Phosphodiesterase-4 Inhibitors: 
      Potential Relevance for the Treatment of Respiratory Diseases.
LID - 10.3390/pharmaceutics15092254 [doi]
LID - 2254
AB  - Inhibitors of phosphodiesterase-4 (PDE4) are small-molecule drugs that, by 
      increasing the intracellular levels of cAMP in immune cells, elicit a broad 
      spectrum of anti-inflammatory effects. As such, PDE4 inhibitors are actively 
      studied as therapeutic options in a variety of human diseases characterized by an 
      underlying inflammatory pathogenesis. Dendritic cells (DCs) are checkpoints of 
      the inflammatory and immune responses, being responsible for both activation and 
      dampening depending on their activation status. This review shows evidence that 
      PDE4 inhibitors modulate inflammatory DC activation by decreasing the secretion 
      of inflammatory and Th1/Th17-polarizing cytokines, although preserving the 
      expression of costimulatory molecules and the CD4+ T cell-activating potential. 
      In addition, DCs activated in the presence of PDE4 inhibitors induce a 
      preferential Th2 skewing of effector T cells, retain the secretion of 
      Th2-attracting chemokines and increase the production of T cell regulatory 
      mediators, such as IDO1, TSP-1, VEGF-A and Amphiregulin. Finally, PDE4 inhibitors 
      selectively induce the expression of the surface molecule 
      CD141/Thrombomodulin/BDCA-3. The result of such fine-tuning is immunomodulatory 
      DCs that are distinct from those induced by classical anti-inflammatory drugs, 
      such as corticosteroids. The possible implications for the treatment of 
      respiratory disorders (such as COPD, asthma and COVID-19) by PDE4 inhibitors will 
      be discussed.
FAU - Nguyen, Hoang Oanh
AU  - Nguyen HO
AD  - ImmunoConcEpT, CNRS UMR 5164, University of Bordeaux, 33000 Bordeaux, France.
FAU - Tiberio, Laura
AU  - Tiberio L
AUID- ORCID: 0000-0003-0482-9898
AD  - Department of Molecular and Translational Medicine, University of Brescia, 25123 
      Brescia, Italy.
FAU - Facchinetti, Fabrizio
AU  - Facchinetti F
AD  - Department of Experimental Pharmacology and Translational Science, Corporate 
      Pre-Clinical R&D, Chiesi Farmaceutici S.p.A., 43122 Parma, Italy.
FAU - Ripari, Giulia
AU  - Ripari G
AD  - Department of Molecular and Translational Medicine, University of Brescia, 25123 
      Brescia, Italy.
FAU - Violi, Valentina
AU  - Violi V
AD  - Department of Molecular and Translational Medicine, University of Brescia, 25123 
      Brescia, Italy.
FAU - Villetti, Gino
AU  - Villetti G
AD  - Department of Experimental Pharmacology and Translational Science, Corporate 
      Pre-Clinical R&D, Chiesi Farmaceutici S.p.A., 43122 Parma, Italy.
FAU - Salvi, Valentina
AU  - Salvi V
AD  - Department of Molecular and Translational Medicine, University of Brescia, 25123 
      Brescia, Italy.
FAU - Bosisio, Daniela
AU  - Bosisio D
AUID- ORCID: 0000-0001-6276-5365
AD  - Department of Molecular and Translational Medicine, University of Brescia, 25123 
      Brescia, Italy.
LA  - eng
GR  - MUR-PRIN 20178ALPCM_005/Italian Ministry of the University and Research/
GR  - Fondi Locali 2020/University of Brescia/
GR  - Fondi Locali 2021/University of Brescia/
PT  - Journal Article
PT  - Review
DEP - 20230831
PL  - Switzerland
TA  - Pharmaceutics
JT  - Pharmaceutics
JID - 101534003
PMC - PMC10535230
OTO - NOTNLM
OT  - CD80
OT  - CD86
OT  - IL-12
OT  - TNFalpha
OT  - Tanimilast
OT  - cDC1
OT  - cDC2
OT  - monocyte-derived DC
OT  - pDC
OT  - tolerogenic DCs
COIS- This work also received funding from Chiesi Farmaceutici S.p.A., which is 
      currently sponsoring the clinical development of Tanimilast. The funder had the 
      following involvement with the study: contributed to manuscript review and 
      editing, approved decision to publish. F.F. and G.V. also disclose that they are 
      employees of Chiesi Farmaceutici S.p.A.; they do not hold Chiesi Farmaceutici 
      S.p.A. stocks or equity shares.
EDAT- 2023/09/28 06:42
MHDA- 2023/09/28 06:43
PMCR- 2023/08/31
CRDT- 2023/09/28 01:38
PHST- 2023/07/27 00:00 [received]
PHST- 2023/08/23 00:00 [revised]
PHST- 2023/08/29 00:00 [accepted]
PHST- 2023/09/28 06:43 [medline]
PHST- 2023/09/28 06:42 [pubmed]
PHST- 2023/09/28 01:38 [entrez]
PHST- 2023/08/31 00:00 [pmc-release]
AID - pharmaceutics15092254 [pii]
AID - pharmaceutics-15-02254 [pii]
AID - 10.3390/pharmaceutics15092254 [doi]
PST - epublish
SO  - Pharmaceutics. 2023 Aug 31;15(9):2254. doi: 10.3390/pharmaceutics15092254.