PMID- 38149577
OWN - NLM
STAT- MEDLINE
DCOM- 20231228
LR  - 20240106
IS  - 1878-1705 (Electronic)
IS  - 1567-5769 (Linking)
VI  - 125
IP  - Pt A
DP  - 2023 Dec
TI  - Immune modulation via dendritic cells by the effect of Thymosin-alpha-1 on immune 
      synapse in HCMV infection.
PG  - 111103
LID - S1567-5769(23)01429-7 [pii]
LID - 10.1016/j.intimp.2023.111103 [doi]
AB  - Talpha1 (Thymosin-alpha-1) is a thymus-derived hormone that has been demonstrated to 
      be effective on diverse immune cell subsets. The objective of this study was to 
      determine the in vitro immunomodulatory effect of Talpha1 in human cytomegalovirus 
      (HCMV) infection. Dendritic cells (DCs) were isolated from peripheral blood 
      mononuclear cells (PBMCs) by negative selection and cultured in the presence or 
      absence of Talpha1. The immunophenotyping of DCs was characterised by multiparametric 
      flow cytometry assessing CD40, CD80, TIM-3 and PDL-1 markers, as well as 
      intracellular TNFalpha production. Then, autologous CD4+ or CD8+ T-Lymphocytes (TLs) 
      isolated by negative selection from PBMCs were co-cultured with DCs previously 
      treated with Talpha1 in the presence or absence of HCMV. Intracellular TNFalpha, IFNgamma, 
      IL-2 production, CD40-L and PD-1 expression were assessed through 
      immunophenotyping, and polyfunctionality in total TLs and memory subsets were 
      evaluated. The results showed that Talpha1 increased CD40, CD80, TIM-3 and TNFalpha 
      intracellular production while decreasing PDL-1 expression, particularly on 
      plasmacytoid dendritic cells (pDCs). Therefore, Talpha1 modulated the production of 
      TNFalpha, IFNgamma and IL-2 in both total and memory subsets of CD4+ and CD8+ TLs by 
      upregulating CD40/CD40-L and downregulating PDL-1/PD-1 expression. Our study 
      concludes that Talpha1 enhances antigen-presenting capacity of DCs, improves TLs 
      responses to HCMV infection, and enhances the polyfunctionality of CD8+ TLs. 
      Consequently, Talpha1 could be an alternative adjuvant for use in therapeutic cell 
      therapy for immunocompromised patients.
CI  - Copyright (c) 2023 The Authors. Published by Elsevier B.V. All rights reserved.
FAU - Espinar-Buitrago, M S
AU  - Espinar-Buitrago MS
AD  - Seccion de Inmunologia, Laboratorio Inmuno-Biologia Molecular (LIBM), Hospital 
      General Universitario Gregorio Maranon (HGUGM), Instituto de Investigacion 
      Sanitaria Gregorio Maranon (IiSGM), 28009 Madrid, Spain; Centro de Investigacion 
      Biomedica en Red Bioingenieria, Biomateriales y Nanotecnologia (CIBER-BBN), 
      Madrid, Spain.
FAU - Vazquez-Alejo, E
AU  - Vazquez-Alejo E
AD  - Seccion de Inmunologia, Laboratorio Inmuno-Biologia Molecular (LIBM), Hospital 
      General Universitario Gregorio Maranon (HGUGM), Instituto de Investigacion 
      Sanitaria Gregorio Maranon (IiSGM), 28009 Madrid, Spain; Centro de Investigacion 
      Biomedica en Red Bioingenieria, Biomateriales y Nanotecnologia (CIBER-BBN), 
      Madrid, Spain.
FAU - Magro-Lopez, E
AU  - Magro-Lopez E
AD  - Seccion de Inmunologia, Laboratorio Inmuno-Biologia Molecular (LIBM), Hospital 
      General Universitario Gregorio Maranon (HGUGM), Instituto de Investigacion 
      Sanitaria Gregorio Maranon (IiSGM), 28009 Madrid, Spain; Centro de Investigacion 
      Biomedica en Red Bioingenieria, Biomateriales y Nanotecnologia (CIBER-BBN), 
      Madrid, Spain.
FAU - Tarancon-Diez, L
AU  - Tarancon-Diez L
AD  - Seccion de Inmunologia, Laboratorio Inmuno-Biologia Molecular (LIBM), Hospital 
      General Universitario Gregorio Maranon (HGUGM), Instituto de Investigacion 
      Sanitaria Gregorio Maranon (IiSGM), 28009 Madrid, Spain; Centro de Investigacion 
      Biomedica en Red Bioingenieria, Biomateriales y Nanotecnologia (CIBER-BBN), 
      Madrid, Spain.
FAU - Leal, M
AU  - Leal M
AD  - Departamento de Medicina Interna, Hospital Viamed Santa Angela de la Cruz, 41014 
      Sevilla, Spain; Hogar Residencia de la Santa Caridad, 41001 Sevilla, Spain.
FAU - Munoz-Fernandez, M A
AU  - Munoz-Fernandez MA
AD  - Seccion de Inmunologia, Laboratorio Inmuno-Biologia Molecular (LIBM), Hospital 
      General Universitario Gregorio Maranon (HGUGM), Instituto de Investigacion 
      Sanitaria Gregorio Maranon (IiSGM), 28009 Madrid, Spain; Centro de Investigacion 
      Biomedica en Red Bioingenieria, Biomateriales y Nanotecnologia (CIBER-BBN), 
      Madrid, Spain. Electronic address: mmunoz.hgugm@salud.madrid.org.
LA  - eng
PT  - Journal Article
DEP - 20231031
PL  - Netherlands
TA  - Int Immunopharmacol
JT  - International immunopharmacology
JID - 100965259
RN  - W0B22ISQ1C (Thymalfasin)
RN  - 61512-21-8 (Thymosin)
RN  - 0 (Hepatitis A Virus Cellular Receptor 2)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (Interleukin-2)
RN  - 0 (Programmed Cell Death 1 Receptor)
SB  - IM
MH  - Humans
MH  - Thymalfasin/pharmacology
MH  - *Thymosin/metabolism
MH  - Hepatitis A Virus Cellular Receptor 2/metabolism
MH  - Leukocytes, Mononuclear/metabolism
MH  - Tumor Necrosis Factor-alpha/metabolism
MH  - Interleukin-2/metabolism
MH  - Programmed Cell Death 1 Receptor/metabolism
MH  - Dendritic Cells
MH  - Synapses
OTO - NOTNLM
OT  - Adjuvant
OT  - CD4+/CD8+ TLs response
OT  - DCs
OT  - HCMV
OT  - Thymosin-alpha-1
COIS- Declaration of Competing Interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2023/12/27 12:41
MHDA- 2023/12/28 06:42
CRDT- 2023/12/27 07:04
PHST- 2023/07/12 00:00 [received]
PHST- 2023/10/18 00:00 [revised]
PHST- 2023/10/18 00:00 [accepted]
PHST- 2023/12/28 06:42 [medline]
PHST- 2023/12/27 12:41 [pubmed]
PHST- 2023/12/27 07:04 [entrez]
AID - S1567-5769(23)01429-7 [pii]
AID - 10.1016/j.intimp.2023.111103 [doi]
PST - ppublish
SO  - Int Immunopharmacol. 2023 Dec;125(Pt A):111103. doi: 
      10.1016/j.intimp.2023.111103. Epub 2023 Oct 31.