Regulatory T Cells And Chemokines For Lymphocyte Recruitment In Cutaneous Lupus Erythematosus

 

Naturally arising CD4+CD25+ regulatory T cells (Treg) represent a major lymphocyte population actively maintaining immunological tolerance to self and non-self-antigens. In the experimental mouse model of LE (NZB/ NZW F1), the frequency of Treg is lower than in control animals. Recently, a decreased number of peripheral Treg was also found in SLE patients and a significant correlation was detected between the number of Treg and disease activity. Whether the suppressive function of Treg cells is impaired in patients with SLE is currently under investigation. Furthermore, a decrease of Treg only at the site of inflammation in skin lesions of patients with CLE has recently been observed. This reduction of Treg in the dermal infiltrate was independent of the subtype of the disease and not reduced in other inflammatory skin diseases such as psoriasis vulgaris. Therefore, a reduction in the number of Treg in skin lesions of patients with CLE might be caused by specific factors of this disease. Nevertheless, studies on CLE did not encompass a general Treg defect as supported by a normal frequency of circulating Treg subpopulation and by a normal capacity to suppress Tcon proliferation. The reduction of Treg in CLE probably reflects a limitation of the disease to the skin, whereas a systemic decrease of Treg might explain the widespread autoimmunity in patients with SLE resulting in multiple organ involvement.

Although the pathogenetic role of skin-infiltrating lymphocytes is undoubted, their recruitment and activation pathways in inflammatory skin diseases, such as CLE, are still elusive. A superfamily of small chemotactic proteins has been shown to regulate lymphocyte trafficking under inflammatory conditions, and it has been demonstrated that UV irradiation induces the expression of T cell attracting chemokines. Furthermore, the CXC chemokine receptor R3 ligands CXCL9, CXCL10, and CXCL11 have been identified as the most abundantly expressed genes in the skin of patients with CLE. Additionally, it has been reported that the CCR4 ligand TARC/CCL17 was strongly expressed in skin lesions and elevated in the serum of patients with CLE. The functional relevance of lymphocytic CCR4 expression could be confirmed by TARC/CCL17-specific in vitro migration assays, suggesting that CCR4 and TARC/CCL17 are involved in the pathophysiology of CLE disease.
Treatment And Prevention Of Cutaneous Lupus Erythematosus
In patients with CLE, it is important to provide instructions concerning methods of protection from sunlight and artificial sources of UV irradiation as well as avoidance of potentially photosensitizing drugs. Topical corticosteroids are the mainstay of treatment for patients with all different subtypes of CLE; however, they are of limited value in the therapy of widespread skin lesions due to well-known side effects, such as skin atrophy. Recently, different groups have found administration of calcineurin inhibitors to be useful in CLE. In addition, physical therapy, such as cryotherapy or lasers and dermatosurgical methods, may be useful adjuncts and can be invaluable in enhancing quality of life for patients with this disease. The mainstay of treatment for widespread skin manifestations in patients with CLE, irrespective of the subtype of this disease, is antimalarial agents. Our understanding of the use of combinations of antimalarial agents and proper dosing according to the ideal body weight limits problems with toxicity. Further therapies, such as dapsone, retinoids, and thalidomide, are helpful for patients with resistant disease; however, side effects need to be taken into consideration. Recent advances in biotechnology resulted in the development of several novel systemic agents for the treatment of autoimmune diseases. It is conceivable that the prevention of apoptotic keratinocytes by protective measures and strategies may significantly reduce disease activity in CLE; however, further progress and controlled clinical trials are necessary for the approval of new therapeutic strategies.

In summary, consequent protection against UV light and also other physical and mechanical injuries may be of significant value for the course and prognosis of CLE, especially since such injuries may even initiate systemic manifestations of the disease, which was previously limited to the skin. Further steps in this research will consider the pathogenetic mechanisms in CLE photosensitivity to develop more specific pharmaceuticals beyond UV filters, such as antioxidants or DNA repair enzymes, which will be able to counteract the detrimental effects of UV irradiation on the disease.

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