AUTHOR=Hu Yifan , Chen Youdong , Chen Zeyu , Zhang Xilin , Guo ChunYuan , Yu ZengYang , Xu Peng , Sun Lei , Zhou Xue , Gong Yu , Yu Qian , Shi Yuling 

TITLE=Dysregulated Peripheral Invariant Natural Killer T Cells in Plaque Psoriasis Patients

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=9

YEAR=2022

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2021.799560

DOI=10.3389/fcell.2021.799560

ISSN=2296-634X

ABSTRACT=<p><bold>Background:</bold> Psoriasis is a common immune-mediated skin disease that involves T-cell-mediated immunity. Invariant natural killer T (<italic>i</italic>NKT) cells are a unique lymphocyte subpopulation that share properties and express surface markers of both NK cells and T cells. Previous reports indicate that <italic>i</italic>NKT cells regulate the development of various inflammatory diseases. IL-17 is a key cytokine in the pathogenesis of psoriasis and a key therapeutic target. Secukinumab is a fully human IgG1κ antibody that targets IL-17A, thereby antagonizing the biological effects of IL-17.</p><p><bold>Objective:</bold> To explore the expression of <italic>i</italic>NKT cells in psoriasis patients and the effect of secukinumab on them.</p><p><bold>Methods:</bold> We examined the frequencies of <italic>i</italic>NKT cells, Tregs, naïve and memory CD4<sup>+</sup>and CD8<sup>+</sup>T cells in the PBMCs as well as their cytokine production in a cohort of 40 patients with moderate-to-severe plaque psoriasis and 40 gender- and age-matched healthy controls. We further collected peripheral blood of another 15 moderate-to-severe plaque psoriasis patients who were treated with secukinumab and evaluated the proportion of <italic>i</italic>NKT cells in the PBMCs at baseline and week 12.</p><p><bold>Results:</bold> The frequencies of conventional CD4<sup>+</sup> T cells, CD8<sup>+</sup> T cells, and Tregs in the PBMCs were comparable between psoriasis patients and healthy controls, but the frequencies of Th17 cells, Tc1 cells and Tc17 cells were increased in psoriasis patients. The frequency of peripheral <italic>i</italic>NKT cells and CD69<sup>+</sup><italic>i</italic>NKT cells was significantly decreased in psoriasis patients. Both <italic>i</italic>NKT2 cells and <italic>i</italic>NKT17 cells were increased in psoriasis patients, but the ratio of <italic>i</italic>NKT2 cells vs <italic>i</italic>NKT17 cells was significantly reduced in psoriasis patients. After receiving secukinumab, the proportion of <italic>i</italic>NKT cells in the PBMCs of patients was increased, while the proportion of <italic>i</italic>NKT17 cells was decreased.</p><p><bold>Conclusion:</bold> Dysregulated <italic>i</italic>NKT cells may be involved in the pathogenesis of psoriasis and secukinumab may play a regulatory role on <italic>i</italic>NKT cells.</p>