Mucosal-Associated Invariant T Cell Deficiency in Systemic Lupus Erythematosus Is Realted to an Intrinsic Defect in the Ca2+/Calcineurin/NFAT1 Signaling Pathway

Yong-Wook Park¹, Young-Nan Cho², Hye-Mi Jin¹, Tae-Jong Kim³ and Seung-Jung Kee⁴, ¹Rheumatology, Chonnam National University Medical School and Hospital, Gwangju, Korea, Republic of (South), ²Rheumatology, Chonnam National University Hospital and Medical School, Gwangju, MN, Korea, Republic of (South), ³Chonnam Nat`l University Medical School&Hospital, Chonnam, Korea, Republic of (South), ⁴Laboratory Medicine, Chonnam National University Medical School and Hospital, Gwangju, Korea, Republic of (South)

Meeting: ACR/ARHP Annual Meeting 2017

Date of first publication: September 18, 2017

Keywords: Disease Activity, innate immunity, mucosal T cells and systemic lupus erythematosus (SLE), T cells

Session Information

Date: Monday, November 6, 2017

Title: Innate Immunity and Rheumatic Disease Poster II

Session Type: ACR Poster Session B

Session Time: 9:00AM-11:00AM

Background/Purpose: 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. Here, we examined the level and function of MAIT cells in patients with rheumatic diseases.

Methods: Patients with systemic lupus erythematosus (SLE; n = 54), rheumatoid arthritis (RA; n = 66), Behçet’s disease (n = 9), ankylosing spondylitis (n = 21), and healthy controls (n = 136) were enrolled in the study. MAIT cell, cytokine and programmed death-1 (PD-1) levels were measured by flow cytometry.

Results: Circulating MAIT cell levels were significantly reduced in systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) 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 (SLEDAI) and 28-joint disease activity score (DAS28). Interestingly, MAIT cell frequency was significantly correlated with natural killer T (NKT) cell frequency in SLE patients. IFN-gamma in MAIT cells was impaired in SLE patients, which was due to an intrinsic defect in the Ca2+/calcineurin/NFAT1 signaling pathway. In SLE patients, MAIT cells were poorly activated by alphagalactosylceramide-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 RA patients, MAIT cell levels were significantly higher in synovial fluid than in peripheral blood.

Conclusion: 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.

Disclosure: Y. W. Park, None; Y. N. Cho, None; H. M. Jin, None; T. J. Kim, None; S. J. Kee, None.

To cite this abstract in AMA style:

Park YW, Cho YN, Jin HM, Kim TJ, Kee SJ. Mucosal-Associated Invariant T Cell Deficiency in Systemic Lupus Erythematosus Is Realted to an Intrinsic Defect in the Ca2+/Calcineurin/NFAT1 Signaling Pathway [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/mucosal-associated-invariant-t-cell-deficiency-in-systemic-lupus-erythematosus-is-realted-to-an-intrinsic-defect-in-the-ca2calcineurinnfat1-signaling-pathway/. Accessed .

ACR Meeting Abstracts - https://acrabstracts.org/abstract/mucosal-associated-invariant-t-cell-deficiency-in-systemic-lupus-erythematosus-is-realted-to-an-intrinsic-defect-in-the-ca2calcineurinnfat1-signaling-pathway/