Cytokines/chemokines

Oral

Lupus Skin Is Characterized by a Robust Type I Interferon Signature Driven in Part by Epidermal Production of Interferon Kappa and Skewed Interferon Responses in Lupus Keratinocytes

Friday, June 16
6:15 PM - 7:30 PM

Cutaneous lupus erythematosus (CLE) rashes are disfiguring and often refractory to usual lupus therapies. A prominent and pathogenic feature of CLE is robust upregulation of type I interferon (IFN)-regulated genes, yet the drivers of this signature are poorly understood in the skin. Using microarray analysis of 90 CLE lesions, we confirmed a prominent type I IFN signature for both discoid and subacute cutaneous lupus characterized by a transcriptional network surrounding STAT1 overexpression. To determine which type I IFNs were driving this IFN signature, we analyzed expression of all type I IFN genes in CLE lesional and control skin. Only two type I IFN transcripts were upregulated in CLE: IFNα10, presumably produced by plasmacytoid dendritic cells recruited to the dermis, and IFNκ, a keratinocyte-produced type I IFN. Immunofluorescence identified IFNκ as robustly produced in CLE epithelium compared to control skin. Both IFNα and IFNκ induced expression of IFN signature genes (MX1, OAS1, IRF7) in control and CLE keratinocytes. However, evaluation of genome-wide response to type I IFNs via RNA sequencing identified a distinct population of transcripts that were highly upregulated in CLE vs. control keratinocytes. Comparison of this unique mRNA population with CLE lesional microarray data identified the majority of CLE-IFN-skewed keratinocyte genes as also altered in CLE lesions. These data support a role for the epidermis in both production of and abnormal response to type I IFNs in CLE and provide a mechanism for the promising effects of type I IFN receptor blockade for CLE.

Celine C. Berthier

University of Michigan

Presentation(s):

    Send Email for Celine Berthier

    Lam Tsoi

    University of Michigan

    Presentation(s):

      Send Email for Lam Tsoi

      Grace Hile

      University of Michigan

      Presentation(s):

        Send Email for Grace Hile

        Mrinal Sarkar

        University of Michigan

        Presentation(s):

          Send Email for Mrinal Sarkar

          Tamra Reed

          University of Michigan

          Presentation(s):

            Send Email for Tamra Reed

            Johann Gudjonsson

            University of Michigan

            Presentation(s):

              Send Email for Johann Gudjonsson

              J. Michelle Kahlenberg

              Assistant Professor of Internal Medicine
              University of Michigan

              Presentation(s):

                Send Email for J. Michelle Kahlenberg


                Assets

                Lupus Skin Is Characterized by a Robust Type I Interferon Signature Driven in Part by Epidermal Production of Interferon Kappa and Skewed Interferon Responses in Lupus Keratinocytes



                Attendees who have favorited this

                Send Email for Lupus Skin Is Characterized by a Robust Type I Interferon Signature Driven in Part by Epidermal Production of Interferon Kappa and Skewed Interferon Responses in Lupus Keratinocytes