PMID- 34428762
OWN - NLM
STAT- MEDLINE
DCOM- 20220406
LR  - 20220716
IS  - 1662-8128 (Electronic)
IS  - 1662-811X (Print)
IS  - 1662-811X (Linking)
VI  - 14
IP  - 2
DP  - 2022
TI  - T-Cell Immune Imbalance in Rheumatoid Arthritis Is Associated with Alterations in 
      NK Cells and NK-Like T Cells Expressing CD38.
PG  - 148-166
LID - 10.1159/000516642 [doi]
AB  - BACKGROUND: CD38+ NK (CD3- CD16+ CD38+ CD56+) cells were increased in rheumatoid 
      arthritis (RA), which suppressed Treg cell differentiation. This study explored 
      how CD38+ NK cells regulated CD4+ T-cell differentiation into Treg cells in RA. 
      METHODS: Proportions of CD38+ NK cells and their counterpart CD38+ NK-like T 
      (CD3+ CD16+ CD38+ CD56+) cells were measured in RA and rats with collagen-induced 
      arthritis (CIA). CD38+ NK cells and CD38+ NK-like T cells were cocultured with 
      CD4+ T cells, respectively. RESULTS: A significantly increased proportion of 
      CD38+ NK cells and a decreased proportion of CD38+ NK-like T cells were detected 
      in RA and CIA blood and synovial fluids. When CD4+ T cells were cocultured with 
      CD38+ NK cells, mammalian target of rapamycin (mTOR) signaling was activated, and 
      Th1/Th2 and Th17/Treg ratios were increased. When CD38+ NK cells were pretreated 
      with anti-CD38 antibody, Treg cell proportion was increased, and Th1/Th2 and 
      Th17/Treg ratios were decreased. CD38+ NK-like T cells showed the opposite 
      results. CD38+ NK cells and CD38+ NK-like-T cells activated differential gene 
      expressions and pathways in CD4+ T cells and initiated Th1 and Th2 cell 
      differentiation by differential gene nodes. CONCLUSIONS: This study suggest that 
      the high CD38+ NK cell proportion and low CD38+ NK-like T cell proportion in RA 
      suppress Treg cell differentiation by stimulating mTOR signaling in CD4+ T cells, 
      which consequentially disturbs the immune tolerance.
CI  - (c) 2021 The Author(s) Published by S. Karger AG, Basel.
FAU - Wang, Hongxing
AU  - Wang H
AD  - Medical Research Center of The Affiliated Hospital of Qingdao University, 
      Qingdao, China.
AD  - Clinical Laboratory of Qilu Hospital, Shandong University, Jinan, China.
FAU - Fang, Kehua
AU  - Fang K
AD  - Clinical Laboratory of The Affiliated Hospital of Qingdao University, Qingdao, 
      China.
FAU - Yan, Weining
AU  - Yan W
AD  - Joint Surgery Department of The Affiliated Hospital of Qingdao University, 
      Qingdao, China.
FAU - Chang, Xiaotian
AU  - Chang X
AD  - Medical Research Center of The Affiliated Hospital of Qingdao University, 
      Qingdao, China.
AD  - Qingdao Engineering Technology Center for Major Disease Marker, Qingdao, China.
LA  - eng
PT  - Journal Article
DEP - 20210824
PL  - Switzerland
TA  - J Innate Immun
JT  - Journal of innate immunity
JID - 101469471
RN  - 0 (Membrane Glycoproteins)
RN  - EC 3.2.2.5 (ADP-ribosyl Cyclase)
RN  - EC 3.2.2.5 (Cd38 protein, rat)
RN  - EC 3.2.2.6 (ADP-ribosyl Cyclase 1)
SB  - IM
MH  - ADP-ribosyl Cyclase/metabolism
MH  - ADP-ribosyl Cyclase 1/metabolism
MH  - Animals
MH  - *Arthritis, Experimental/metabolism
MH  - *Arthritis, Rheumatoid/metabolism
MH  - Killer Cells, Natural
MH  - Membrane Glycoproteins/metabolism
MH  - Rats
MH  - T-Lymphocytes, Regulatory
MH  - Th17 Cells
PMC - PMC9082181
OTO - NOTNLM
OT  - CD38+ NK cells
OT  - CD38+ NK-like T cells
OT  - Cluster of differentiation 38
OT  - Collagen-induced arthritis
OT  - Immune tolerance
OT  - Rheumatoid arthritis
OT  - Treg cells
COIS- The authors declare that they have no competing interests.
EDAT- 2021/08/25 06:00
MHDA- 2022/04/07 06:00
PMCR- 2021/08/24
CRDT- 2021/08/24 20:27
PHST- 2020/06/16 00:00 [received]
PHST- 2021/04/18 00:00 [accepted]
PHST- 2021/08/25 06:00 [pubmed]
PHST- 2022/04/07 06:00 [medline]
PHST- 2021/08/24 20:27 [entrez]
PHST- 2021/08/24 00:00 [pmc-release]
AID - 000516642 [pii]
AID - jin-0014-0148 [pii]
AID - 10.1159/000516642 [doi]
PST - ppublish
SO  - J Innate Immun. 2022;14(2):148-166. doi: 10.1159/000516642. Epub 2021 Aug 24.