role-of-cytokines

IFN-1 plays a critical role in the pathogenesis of SLE and promotes the cytolytic activities of NK cells and cytotoxic T cells, which lead to tissue damage.¹

Cytokines are secreted by different immune cells such as lymphocytes, macrophages and dendritic cells (DC), and modulate the activation and/or functions of several target cells in both the innate and the adaptive immune systems.²
An abnormal function of the DC can promote dysregulated T and B cell functions, and in SLE the DC may play a crucial role in the disease pathogenesis through the production of IFN-α.²
A role for IFN- α in the initiation of SLE also comes from the observation that therapeutic administration of this cytokine to patients with viral infection or tumors can induce autoantibodies and, occasionally, lupus2
the biological effects of IFNs are mediated through the Jak/STAT pathway, where both IFN- α / β and IFN- α activate the transcription factor STAT1. Of note, the expression and activation of STAT1 are significantly increased in lupus2
Since TNF- α regulates the production of IFN- α by pDC , neutralization of TNF in patients undergoing anti-TNF therapy could possibly sustain the production of IFN- α by pDC and, without the negative regulation of IFN- α secretion, the overproduction of this cytokine could promote autoimmunity.2 Genetic factors, environmental factors and hormonal factors are believed to contribute to the occurrence of SLE.³

IFN-1, type 1 interferon; IFNAR, subunit 1 of the type 1 interferon receptor; pDC, plasmacytoid dendritic cell; SLE, systemic lupus erythematosus.

Learn about the clinical significance of IFN-1

References:

1. Kim JM, Park SH, Kim HY, Kwok SK. A Plasmacytoid Dendritic Cells-Type I Interferon Axis Is Critically Implicated in the Pathogenesis of Systemic Lupus Erythematosus. Int J Mol Sci. 2015;16(6):14158- 14170.
2. Lourenco V. Elaine and Cava La Antonio, Cytokines in Systemic Lupus Erythematosus, Current Molecular Medicine 2009; 9 (3) . https://dx.doi.org/10.2174/156652409787847263.
3. Pan, L. et al. (2019) ‘Immunological pathogenesis and treatment of systemic lupus erythematosus’, World Journal of Pediatrics, 16(1), pp. 19–30. doi:10.1007/s12519-019-00229-3.

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THE IMMUNOPATHOGENIC CYCLE OF SLE