Reading Comprehension (RC) | Systemic lupus ethematosus (SLE) is an autoimmune disease characterize

Systemic lupus ethematosus (SLE) is an autoimmune disease characterized by the aberrant and chronic stimulation of the innate immune system—our first line of defense against infection. Under normal circumstances, immune cells are recruited to sites of infection through the production of chemical factors called cytokines. In patients with SLE, cytokines recruit cells to attack normal, healthy tissues without the presence of an infectious pathogen. This results in the proliferation of antibody-immune complexes that cause inflammation and damage to the kidneys, blood vessels, and skin.

Patients with SLE are often treated with courses of strong immunosupressive drugs, such as cytotoxic drugs, antimalarial compounds and glucocorticoids. While glucocorticoid therapy is considered the most effective course of treatment, it is regrettably transient, requiring more aggressive (and potentially more harmful) treatments, such as high-dose methylprednisolone pulse therapy. Discovering why glucocorticoid therapy fails to provide lasting relief has been the subject of numerous recent studies. The main culprit seems to be the plasmacytoid dendritic cells (pDC)—innate immune cells that circulate in the blood and are found in the peripheral lymphoid organs. While pDCs are normally susceptible to treatment with glucocorticoids, they are resistant to such treatment in patients with SLE. And, since pDCs are responsible for producing the key cytokines involved in SLE pathogenesis, the level of thesecytokines does not substantially decrease with treatment, and symptoms quickly relapse. The precise mechanism by which pDC resistance occurs is still unknown.