PMID- 37073709
OWN - NLM
STAT- MEDLINE
DCOM- 20230607
LR  - 20230613
IS  - 1582-4934 (Electronic)
IS  - 1582-1838 (Print)
IS  - 1582-1838 (Linking)
VI  - 27
IP  - 11
DP  - 2023 Jun
TI  - M2-like macrophages polarized by Foxp3(-) Treg-of-B cells ameliorate 
      imiquimod-induced psoriasis.
PG  - 1477-1492
LID - 10.1111/jcmm.17748 [doi]
AB  - Our group have demonstrated that splenic B cells contributed to the CD4(+) 
      CD25(-) naive T cells conversion into CD4(+) CD25(+) Foxp3(-) regulatory T cells 
      without adding appended cytokines, named Treg-of-B cells which were potent 
      suppressors of adaptive immunity. We like to investigate whether Treg-of-B cells 
      could promote alternatively activated macrophage (M2 macrophages) polarization 
      and alleviate inflammatory disease, psoriasis. In this study, we co-cultured the 
      bone marrow-derived macrophages (BMDMs) with Treg-of-B cells under LPS/IFN-gamma 
      stimulation and analyzed the M2-associated gene and protein using qPCR, western 
      blotting, and immunofluorescence staining. We also examined the therapeutic 
      effect of Treg-of-B cell-induced M2 macrophage for skin inflammation using 
      imiquimod (IMQ)-induced psoriatic mouse model. Our results showed that BMDMs 
      co-cultured with Treg-of-B cells upregulated typical M2-associated molecules, 
      including Arg-1, IL-10, Pdcd1lg2, MGL-1, IL-4, YM1/2 and CD206. In an 
      inflammatory environment, TNF-alpha and IL-6 production by macrophages co-cultured 
      with Treg-of-B cells was decreased significantly. The molecular mechanism 
      revealed that Treg-of-B cells promoted M2 macrophage polarization via STAT6 
      activation in a cell contact-dependent manner. Moreover, the treatment with 
      Treg-of-B cell-induced M2 macrophages attenuated the clinical manifestations of 
      psoriasis, such as scaling, erythema and thickening in the IMQ-induced psoriatic 
      mouse model. T cell activation in draining lymph nodes was decreased in the 
      Treg-of-B cell-induced M2 macrophage group after IMQ application. In conclusion, 
      our findings suggested that Foxp3(-) Treg-of-B cells could induce alternatively 
      activated M2 macrophages through STAT6 activation, providing a cell-based 
      therapeutic strategy for psoriasis.
CI  - (c) 2023 The Authors. Journal of Cellular and Molecular Medicine published by 
      Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.
FAU - Huang, Jing-Hui
AU  - Huang JH
AD  - Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan 
      University, Taipei, Taiwan.
FAU - Lin, Yu-Li
AU  - Lin YL
AD  - Department of Medical Research, National Taiwan University Hospital, Taipei, 
      Taiwan.
FAU - Wang, Li-Chieh
AU  - Wang LC
AD  - Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan.
FAU - Chiang, Bor-Luen
AU  - Chiang BL
AUID- ORCID: 0000-0002-6705-0286
AD  - Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan 
      University, Taipei, Taiwan.
AD  - Department of Medical Research, National Taiwan University Hospital, Taipei, 
      Taiwan.
AD  - Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan.
AD  - Graduate Institute of Immunology, College of Medicine, National Taiwan 
      University, Taipei, Taiwan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230419
PL  - England
TA  - J Cell Mol Med
JT  - Journal of cellular and molecular medicine
JID - 101083777
RN  - P1QW714R7M (Imiquimod)
RN  - 0 (Cytokines)
RN  - 0 (Foxp3 protein, mouse)
RN  - 0 (Forkhead Transcription Factors)
SB  - IM
MH  - Mice
MH  - Animals
MH  - Imiquimod/adverse effects
MH  - *T-Lymphocytes, Regulatory/metabolism
MH  - *Psoriasis/chemically induced/drug therapy
MH  - Macrophages/metabolism
MH  - Cytokines/metabolism
MH  - Forkhead Transcription Factors/metabolism
PMC - PMC10243160
OTO - NOTNLM
OT  - M2 macrophage
OT  - STAT6
OT  - Treg-of-B cells
OT  - imiquimod
OT  - psoriasis
COIS- The authors have declared no competing interests exist.
EDAT- 2023/04/19 06:41
MHDA- 2023/06/07 06:42
PMCR- 2023/04/19
CRDT- 2023/04/19 04:43
PHST- 2023/03/13 00:00 [revised]
PHST- 2022/12/13 00:00 [received]
PHST- 2023/04/05 00:00 [accepted]
PHST- 2023/06/07 06:42 [medline]
PHST- 2023/04/19 06:41 [pubmed]
PHST- 2023/04/19 04:43 [entrez]
PHST- 2023/04/19 00:00 [pmc-release]
AID - JCMM17748 [pii]
AID - 10.1111/jcmm.17748 [doi]
PST - ppublish
SO  - J Cell Mol Med. 2023 Jun;27(11):1477-1492. doi: 10.1111/jcmm.17748. Epub 2023 Apr 
      19.