PMID- 38159177
OWN - NLM
STAT- Publisher
LR  - 20231230
IS  - 1573-2576 (Electronic)
IS  - 0360-3997 (Linking)
DP  - 2023 Dec 30
TI  - MALT1 Protease Regulates T-Cell Immunity via the mTOR Pathway in Oral Lichen 
      Planus.
LID - 10.1007/s10753-023-01952-w [doi]
AB  - Oral lichen planus (OLP) is a T cell-mediated immune mucosal disease of unknown 
      pathogenesis. Whether mucosa-associated lymphoid tissue lymphoma translocation 
      protein 1 (MALT1), an intracellular signaling protein, is involved in the T-cell 
      immune dysfunction of OLP remains elusive. MALT1 expression in local and 
      peripheral T cells of OLP and controls was analyzed using immunohistochemistry, 
      multiplex immunohistochemistry, and flow cytometry. The expression of MALT1 in 
      activated Jurkat T cells incubated with either OLP plasma or interleukin 
      (IL)-7/IL-15 was determined by flow cytometry. The effects of MALT1 and 
      mechanistic target of rapamycin (mTOR) on T-cell immunity were investigated 
      through western blot, CCK8 assay, and flow cytometry. The expression of MALT1 
      protein was elevated in local OLP T cells and mucosal-associated invariant T 
      (MAIT) cells, while reduced in peripheral OLP T cells, MAIT cells, and follicular 
      helper-like MAIT (MAITfh) cells. Stimulation with OLP plasma and IL-7/ IL-15 had 
      no effect on MALT1 expression in activated Jurkat T cells. MALT1 
      protease-specific inhibitor (MI-2) induced mTOR phosphorylation, increased B-cell 
      lymphoma 10 (BCL10) expression, inhibited T-cell proliferation, and promoted 
      T-cell apoptosis. The combination of MI-2 and rapamycin increased MALT1 
      expression, further suppressed T-cell proliferation, and facilitated T-cell 
      apoptosis. MALT1 expression is aberrant in both local lesions and peripheral 
      blood of OLP. Inhibition of the mTOR pathway further enhances the suppression of 
      T-cell proliferation and the promotion of apoptosis induced by the MALT1 
      inhibitor MI-2.
CI  - (c) 2023. The Author(s), under exclusive licence to Springer Science+Business 
      Media, LLC, part of Springer Nature.
FAU - Wang, Xiao-Feng
AU  - Wang XF
AD  - State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key 
      Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of 
      Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, China.
FAU - Wang, Fang
AU  - Wang F
AD  - State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key 
      Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of 
      Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, China.
AD  - Department of Oral Medicine, School and Hospital of Stomatology, Wuhan 
      University, Luoyu Road 237, Wuhan, 430079, China.
FAU - Zhou, Gang
AU  - Zhou G
AD  - State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key 
      Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of 
      Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, China. 
      zhougang@whu.edu.cn.
AD  - Department of Oral Medicine, School and Hospital of Stomatology, Wuhan 
      University, Luoyu Road 237, Wuhan, 430079, China. zhougang@whu.edu.cn.
LA  - eng
GR  - No. 81970949/National Natural Science Foundation of China/
GR  - No. 81970949/National Natural Science Foundation of China/
GR  - No. 81970949/National Natural Science Foundation of China/
PT  - Journal Article
DEP - 20231230
PL  - United States
TA  - Inflammation
JT  - Inflammation
JID - 7600105
SB  - IM
OTO - NOTNLM
OT  - Mucosa-associated lymphoid tissue lymphoma translocation protein 1
OT  - Mucosal-associated invariant T cells.
OT  - Oral lichen planus
OT  - T cells
OT  - mTOR
EDAT- 2024/01/02 11:42
MHDA- 2024/01/02 11:42
CRDT- 2023/12/30 11:06
PHST- 2023/11/08 00:00 [received]
PHST- 2023/12/15 00:00 [accepted]
PHST- 2023/12/12 00:00 [revised]
PHST- 2024/01/02 11:42 [medline]
PHST- 2024/01/02 11:42 [pubmed]
PHST- 2023/12/30 11:06 [entrez]
AID - 10.1007/s10753-023-01952-w [pii]
AID - 10.1007/s10753-023-01952-w [doi]
PST - aheadofprint
SO  - Inflammation. 2023 Dec 30. doi: 10.1007/s10753-023-01952-w.