Understanding the immune mechanism is essential for the treatment of diseases. Psoriasis is an inflammatory skin disease that is mediated by cells and molecules of the innate and adaptive immune systems22. Disorders of innate and adaptive skin immune responses result in the development and maintenance of psoriasis inflammation30. In some cases, the skin immune response is no longer limited to the skin, leading to systemic chronic inflammation and then to the development of comorbidities31. For example, metabolic syndrome (diabetes, arterial hypertension, dyslipidemia and obesity), cardiovascular disease, depression, and thrombus-related diseases are all related to chronic inflammation of psoriatic skin32–34. Therefore, it is very important to study the immune mechanism of psoriasis to control the occurrence and development of the disease.
Although MAIT cells play an important role in the formation of the immune defense barrier, their function in the occurrence and development of autoimmune diseases is complex. One study reported that the number of CD3 + TCRVα7.2 + CD161 + cells in the peripheral blood of patients with acute and convalescent rheumatic fever increased significantly, and these cells could produce more IFN-γ, TNF-α, perforin, etc.35. It is well known that these factors can aggravate the progression of psoriasis36. The abnormal activation of dendritic cells in psoriatic skin leads to the production of TNF-α, which can promote the development of psoriasis dermatitis by activating keratinocytes37. In the clinic, the application of TNF-α inhibitors has achieved positive results in the treatment of psoriasis38. However, it is interesting that inhibition of TNF-α may also induce psoriasis39. Therefore, the increase in MAIT in circulation may be related to disease and may be the result of multiple factors. However, it is difficult to determine whether MAIT cells are more mature in the thymus and whether there are more peripheral clones or less apoptotic cells. Generally, the development of MAIT cells requires stimulation by a peripheral symbiotic antigen. Psoriasis, an autoimmune disease, is the result of abnormal reactions of the immune system and is associated with the occurrence and development of the disease. One study demonstrated that the subsequent expansion and maintenance of the MAIT-17/1 response depended on IL-23, and the combined inoculation of IL-23 and 5-OP-RU enhanced the control of Legionella pneumoniae infection mediated by MAIT cells40. In addition, another study observed that cells in the synovial fluid and peripheral blood MAIT cells of patients with psoriatic arthritis express the IL-23 receptor. After stimulation, IL-23R upregulation was observed in these cells25. IL-23 is synthesized by macrophages and dendritic cells in response to the stimulation of Toll-like receptors and C-type lectin receptors41. IL-23 can promote and maintain the production of IL-1740, 42. In MAIT cells, TNF-α is also an inducer of IL-23, and inhibitors clinically targeted at TNF-α, IL-23 and IL-17 have been shown to be effective in the selective treatment of psoriasis32, 43. Therefore, it can be inferred that the increase in MAIT cells in patients with psoriasis may be related to the abnormal expression of immune factors in these patients.
MAIT activation was positively correlated with disease severity17. We chose CD69 as the marker of MAIT activation. CD69 transcription started as early as 30 minutes to 1 hour after T lymphocyte activation and could be detected 2–3 hours after stimulation, and the level of CD69 decreased after 4–6 hours44. Although our results revealed no difference between activated CD3 + MAIT cells in psoriasis patients and the healthy control group, the total number of CD3 + MAIT cells increased, indicating that the number of functional MAIT cells in patients with psoriasis increased. In addition, activated CD8 + MAIT increased. This finding is consistent with previous studies25 and indicates that MAIT cells of psoriasis patients are always stimulated and activated. It should be noted that CD8 + MAIT cells are more suitable for proinflammatory functions and can produce more proinflammatory cytokines and exhibit greater cytotoxicity potential45 .This is consistent with our findings.
Interleukin-17A (IL-17A) is one of the main mediators of tissue inflammation in many autoimmune diseases46. Studies have shown that MAIT is an important source of IL-1741, 47. IL-17A acts on various cell targets, including keratinocytes, neutrophils, endothelial cells, fibroblasts, osteoclasts, chondrocytes and osteoblasts, to stimulate the production of various antimicrobial peptides, chemokines and proinflammatory and proliferative cytokines, which subsequently promote tissue inflammation and bone remodeling48. Studies have confirmed that the increased production of IL-17 by MAIT cells in patients with psoriasis49. In the absence of exogenous antigens, MAIT cells are activated by INF-α, IL-15, IL-12 and IL-1817, 50, 51. In particular, CD8 + MAIT cells exhibit increased levels of IL-12 and IL-18 receptors as well as activated CD2, CD9 and NKG2D receptors52. In addition, one new study showed that TL1A is increased in a psoriasis mouse model53 and has synergistic effects with IL-17 and other factors. Another study showed that IL1A can stimulate MAIT activation54. Therefore, the activation of MAIT cells in patients with psoriasis is the result of multiple factors. Studies have shown that the proportion of failed phenotype MAIT cells in autoimmune diseases increases, and the cells ultimately die due to overactivation16, 17. These studies can explain the differences between our results and other studies. For example, Vera et al.26 showed that the typical case control of CD4-CD8 + MAIT cells was not related. This result may be attributed to the fact that the method that firmly distinguishes different subtypes of CD8 cells. Charles et al.16 showed that the MAIT cell frequency was not affected in patients with psoriasis, which may be related to the fact that only 7 patients in this study had severe psoriasis.
In conclusion, our study shows that the MAIT cell phenotype is abnormal in patients with psoriasis and may be involved in the development of the disease. These abnormalities may lead to skin and systemic immune disorders in patients with psoriasis.