Dermatomyositis and Type 1 Interferons

Greenberg, Steven A.

doi:10.1007/s11926-010-0101-6

Cited by 102 publications

(74 citation statements)

References 35 publications

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“…These findings support a crucial role for type I interferons in pathological features of DM [56]. One of the well-known mechanism that induces type I IFN production is the trigger of toll-like receptors (TLR7 and 9) in plasmacytoid dendritic cells (pDCs), specialized in the production of type I IFN, which resulted abundant both in the skin lesions of SLE patients and in the affected muscle cells of DM patients [48,57].…”

Section: Dysregulated Interferon Pathway In Lupus and Other Multifactsupporting

confidence: 71%

Reappraisal of Antimalarials in Interferonopathies: New Perspectives for Old Drugs

Piscianz

Cuzzoni

Sharma

et al. 2018

CMC

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The story of antimalarials as antinflammatory drugs dates back few centuries. Chinin, the extract of the Cinchona bark, has been exploited since the 18th century for its antimalarial and antifebrile properties. Later, during the Second World War, the broad use of antimalarials allowed arguing their antirheumatic effect on soldiers. Since then, these drugs have been broadly used to treat Systemic Lupus Erythematosus, but, only recently, the molecular mechanisms of action have been partly clarified.The inhibitory action on vacuole function and trafficking has been considered for decades the main mechanism of the action of antimalarials, affecting the activation of phagocytes and dendritic cells. In addition, chloroquine is also as a potent inhibitor of autophagy, providing another possible explanation of its antinflammatory action. However, much attention has been recently devoted to the action of antimalarials on the so-called cGAS-STING pathway deputed to the sensing of nucleic acid and to the production of type 1 interferons. This pathway is a fundamental mechanism for host defence, since it is able to detect microbial DNA and RNA and induce the immune response that will lead to the production of interferons. Of note, genetic defects in disposal of nucleic acids lead to inappropriate activation of the cGAS-STING pathway and inflammation. These disorders, named type I interferonopathies, represent a valuable model to study the antinflammatory potential of antimalarials.We will discuss possible development of antimalarials to improve the treatment of type I interferonopathies and, likely multifactorial disorders characterised by interferon inflammation, such as systemic lupus erythematosus.

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Section: Dysregulated Interferon Pathway In Lupus and Other Multifactsupporting

confidence: 71%

Reappraisal of Antimalarials in Interferonopathies: New Perspectives for Old Drugs

Piscianz

Cuzzoni

Sharma

et al. 2018

CMC

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“…In certain cases of juvenile and adult DM, however, excessive tissue infiltrates of CD8 + T cells were observed [4,19]. Meanwhile, recent gene expression analyses demonstrated a strong linkage to an IFN signature in the target tissues of DM [20][21][22], and type-I IFN-producing plasmacytoid dendritic cells markedly infiltrated the muscle of DM patients [23]. These findings indicate that both type 1 and type 2 IFN and Th2 cytokines are expressed in DM.…”

Section: Discussionmentioning

confidence: 99%

Preferential infiltration of interleukin-4-producing CXCR4+ T cells in the lesional muscle but not skin of patients with dermatomyositis

Fujiyama

Ito

Ogawa

et al. 2014

Clinical and Experimental Immunology

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SummaryDermatomyositis (DM) and polymyositis (PM) are collectively termed autoimmune myopathy. To investigate the difference between muscle-and skininfiltrating T cells and to address their role for myopathy, we characterized T cells that were directly expanded from the tissues. Enrolled into this study were 25 patients with DM and three patients with PM. Muscle and skin biopsied specimens were immersed in cRPMI medium supplemented with interleukin ( Our study suggests that T cell populations in the muscle and skin are different, and the Th2 cell infiltrate in the muscle is associated with the low severity of myositis in DM.

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“…These data suggest that IFN-α could play a role in disease initiation in JDM. It is also postulated that there is a common pathogenic mechanism involving type 1 IFN mediation of both muscle and skin inflammation in adult dermatomyositis (DM) [17]. Adult DM and JDM disease activity also seem to correlate with the type 1 IFN gene signature and with the type 1 IFN chemokine signature [18•].…”

Section: Immunologic Mechanismsmentioning

confidence: 99%