| Systemic lupus erythematosus (SLE) is a complex autoimmune disease, characterized by appearance of numerous autoantibodies and multiple organ involvement. IFN-αplays an important role in the pathogenesis of SLE. It is found that the serum level of IFN-αin SLE was significantly increased, and serum IFN-αlevel was positively correlated with the level of anti-dsDNA antibody and disease severity as well as disease activity. IFN-αis mainly secreted by plasmacytoid dendritic cells (pDCs) in human. There are many kinds of autoantibodies and immune complexes composed of self-DNA in SLE patients. The immune complexes activate pDCs to produce large amount of IFN-αwhich work in immuno-injury. hCAP-18/LL-37 is the only member of the antimicrobial peptide cathelicidins family identified in human so far and plays a vital role in cutaneous innate immun. Liu YJ et al found that LL-37 can form complex with DNA released by dying cells, combine with TLR-9 of pDCs, activate pDCs to release IFN-α, and initiate psoriasis. It is not clear that how the self-DNA activate pDCs, whether LL-37 is involved in SLE pathogenesis. In this study, the expression of LL-37, pDCs and IFN-αin SLE skin and LN renal tissue were investigated, and the correlation among them three and their roles were also speculated.This study consists of two sections:Section I:LL-37 expression in the skin of systemic lupus erythematosusThe patients were assigned to the SLE patients group and healthy control group respectively. All the patients neither has cutaneous trauma, inflammation and infection nor had been treated with immunosuppressive and/or glucocorticoid. The expressions of LL-37, pDCs and IFN-αin skin specimens were detected with immunohistochemical technique and in situ hybridization. IH results showed that expression levels of LL-37, pDCs and IFN-α(143.29±6.72, 150.11±9.84,137.00±9.34) were significantly higher in SLE skin than that (203.50±3.43,205.49±3.78,200.70±4.68) in healthy controls. ISH results showed that expression levels of LL-37 and pDCs (153.53±7.49,125.89±7.56) were significantly higher in SLE skin than that (204.10±4.05,201.17±3.47) in healthy controls. There were significant difference among the groups (P<0.01). This study further proved the role of pDCs secreting IFN-αin SLE which were reported in the published literatures, suggesting that LL-37 may work in pathogenesis of SLE.The specimens from SLE patients were cut into serial sections. IH was used to detect the expressions of LL-37, pDCs and IFN-αin three consecutive sections selected from serial sections, respectively. ISH was used to detect the expressions of LL-37 and pDCs in two consecutive sections selected from serial sections, respectively. The results showed that the locations of LL-37, pDCs and IFN-αexpression were almost the same. The correlation analysis was made among the expression levels of LL-37, pDCs and IFN-αin SLE skin, respectively. The results of correlation analysis for IH showed that there was significant positive correlation between the expression level of pDCs and IFN-α(r=0.983, P<0.001), and between LL-37 and pDCs (r=0.951, P<0.001), also between LL-37 and IFN-α(r=0.938, P<0.001). The result of correlation analysis for ISH showed that expression level of LL-37 was significant positive correlated with the expression level of pDCs (r=0.945, P<0.001). These data suggested that LL-37 played a role and may be relevant to pDCs activation and secretion of IFN-αin SLE skin.By the analysis of clinical data, it is found that all the SLE patients recruited in our study were in active disease stage estimated by SLEDAI score. So it is considered that LL-37 was associated with disease activity. The detection of serum anti-dsDNA antibody in 9 SLE patients showed that 7 cases were positive and 2 cases were negative at the time for biopsies. There was no statistically significance in the expression levels of LL-37, pDCs and IFN-αbetween patients with anti-dsDNA antibody positive and those with negative. Consequently, LL-37 may act not only by combination with self-DNA which has been proved, but also possibly by other way to activate pDCs to release IFN-αin skin lesions of SLE. Section II:LL-37 expression in the kidney of Lupus nephritisThe patients were assigned to the LN patients group and control group respectively. The expressions of LL-37, pDCs and IFN-αin renal tissue were detected with immunohistochemical technique and in situ hybridization. IH results showed that expression levels of LL-37, pDCs and IFN-α(116.40±8.01, 140.98±8.86,127.62±9.38) were significantly higher in renal tissue of LN patients than that (198.03±3.77,204.73±3.16,210.40±3.54) in controls. ISH results showed that expression levels of LL-37 and pDCs (145.30±6.29, 79.60±8.59) were significantly higher in renal tissue of LN patients than that (205.10±4.47,199.40±3.73) in controls. There were significant difference among the groups (P<0.01). This study further proved the role of pDCs secreting IFN-αin LN which were reported in the published literatures, suggesting that LL-37 may work in pathogenesis of LN.The specimens from LN patients were cut into serial sections. IH was used to detect the expressions of LL-37, pDCs and IFN-αin three consecutive sections selected from serial sections, respectively. ISH was used to detect the expressions of LL-37 and pDCs in two consecutive sections selected from serial sections, respectively. The results showed that the locations of LL-37, pDCs and IFN-αexpression were almost the same. The correlation analysis was made among the expression levels of LL-37, pDCs and IFN-αin LN kidney, respectively. The results of correlation analysis for IH showed that there was significant positive correlation between the expression level of pDCs and IFN-α(r=0.984, P<0.001), and between LL-37 and pDCs (r=0.983, P<0.001), also between LL-37 and IFN-α(r=0.981, P<0.001). The result of correlation analysis for ISH showed that expression level of LL-37 was significant positive correlated with the expression level of pDCs (r=0.927, P<0.001). These data suggested that LL-37 played a role and may be relevant to pDCs activation and secretion of IFN-αin renal damage of LN.The detection of serum anti-dsDNA antibody in 10 cases LN patients was all positive. The result of renal pathology showed that all the LN patients had deposition of immunoglobulin, and individual patients even had deposition of complement. Thus, it is inferred that self-DNA or immune complexes may combine with LL-37 to activate pDCs to release IFN-αin kidney lesion of LN.The innovation of this study is:First, there was higher expression level of LL-37 in SLE skin and renal tissue of LN for the first time at home and abroad. It is suggested that LL-37 may be one of leading causes for pathogenesis of SLE. Second, it is proved that locations of LL-37, pDCs and IFN-αexpression were almost the same and there was significant positive correlation between the expression level of them (P<0.001) for the first time at home and abroad, suggesting that LL-37 played a role and may be relevant to pDCs activation and secretion of IFN-αin SLE. Finally, immunohistochemical technique and in situ hybridization were used to detecte the expressions of LL-37, pDCs and IFN-αand consecutive sections staining was used to investigated the relationship among them in SLE skin and renal tissue of LN for the first time at home and abroad. This study could contribute to a better understanding of the pathogenesis of SLE.
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