상위피인용논문
- 조회478
Young-Nan Cho,*,1 Seung-Jung Kee,†,1 Tae-Jong Kim,* Hye Mi Jin,* Moon-Ju Kim,* Hyun-Ju Jung,* Ki-Jeong Park,* Sung-Ji Lee,* Shin-Seok Lee,* Yong-Soo Kwon,‡ Hae Jin Kee,§ Nacksung Kim,¶ and Yong-Wook Park*
*Department of Rheumatology, Chonnam National University Medical School and Hospital, Gwangju 501-757, Republic of Korea;
†Department of Laboratory Medicine, Chonnam National University Medical School and Hospital, Gwangju 501-757, Republic of Korea;
‡Department of Pulmonary and Critical Care Medicine, Chonnam National University Medical School and Hospital, Gwangju 501-757, Republic of Korea;
§Heart Research Center, Chonnam National University Hospital, Gwangju 501-757, Republic of Korea;
and ¶ Department of Pharmacology, Chonnam National University Medical School, Gwangju 501-757, Republic of Korea
1Y.-N.C. and S.-J.K. contributed equally to this work.
Correspondence: Dr. Yong-Wook Park
Abstract
Mucosal-associated invariant T (MAIT) cells contribute to protection against certain microorganism infections and play an important role in mucosal immunity. However, the role of MAIT cells remains enigmatic in autoimmune diseases. In this study, we examined the level and function of MAIT cells in patients with rheumatic diseases. MAIT cell, cytokine, and programmed death-1 (PD-1) levels were measured by flow cytometry. Circulating MAIT cell levels were significantly reduced in systemic lupus erythematosus (SLE) and rheumatoid arthritis patients. In particular, this MAIT cell deficiency was more prominent in CD8(+) and double-negative T cell subsets, and significantly correlated with disease activity, such as SLE disease activity index and 28-joint disease activity score. Interestingly, MAIT cell frequency was significantly correlated with NKT cell frequency in SLE patients. IFN-γ production in MAIT cells was impaired in SLE patients, which was due to an intrinsic defect in the Ca(2+)/calcineurin/NFAT1 signaling pathway. In SLE patients, MAIT cells were poorly activated by α-galactosylceramide-stimulated NKT cells, thereby showing the dysfunction between MAIT cells and NKT cells. Notably, an elevated expression of PD-1 in MAIT cells and NKT cells was associated with SLE. In rheumatoid arthritis patients, MAIT cell levels were significantly higher in synovial fluid than in peripheral blood. Our study primarily demonstrates that MAIT cells are numerically and functionally deficient in SLE. In addition, we report a novel finding that this MAIT cell deficiency is associated with NKT cell deficiency and elevated PD-1 expression. These abnormalities possibly contribute to dysregulated mucosal immunity in SLE.
논문정보
- Research article
- 2014년 10월 (BRIC 등록일 2022-11-23)
- 국내 연구진
- 의약학 > 응용의학
- 120회 이상 인용된 논문
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