title: Master regulators of infiltrate recruitment in autoimmune disease identified through network-based molecular deconvolution.
abstract: Network-based molecular modeling of physiological behaviors has proven invaluable in the study of complex diseases such as cancer, but these approaches remain largely untested in contexts involving interacting tissues such as autoimmunity. Here, using Alopecia Areata (AA) as a model, we have adapted regulatory network analysis to specifically isolate physiological behaviors in the skin that contribute to the recruitment of immune cells in autoimmune disease. We use context-specific regulatory networks to deconvolve and identify skin-specific regulatory modules with IKZF1 and DLX4 as master regulators (MRs). These MRs are sufficient to induce AA-like molecular statesin vitroin three cultured cell lines, resulting in induced NKG2D-dependent cytotoxicity. This work demonstrates the feasibility of a network-based approach for compartmentalizing and targeting molecular behaviors contributing to interactions between tissues in autoimmune disease.
authors.affiliation: Department of Dermatology, Herbert Irving Pavilion, Columbia University, 161 Fort Washington Avenue, New York, NY, 10032, USA ; Department of Systems Biology, Columbia University, 1130 Saint Nicholas Avenue, New York, NY, 10032, USA.
authors.forename: James C
authors.initials: JC
authors.lastname: Chen
authors.affiliation: Department of Dermatology, Herbert Irving Pavilion, Columbia University, 161 Fort Washington Avenue, New York, NY, 10032, USA.
authors.forename: Jane E
authors.initials: JE
authors.lastname: Cerise
authors.affiliation: Department of Dermatology, Herbert Irving Pavilion, Columbia University, 161 Fort Washington Avenue, New York, NY, 10032, USA.
authors.forename: Ali
authors.initials: A
authors.lastname: Jabbari
authors.affiliation: Department of Dermatology, Herbert Irving Pavilion, Columbia University, 161 Fort Washington Avenue, New York, NY, 10032, USA.
authors.forename: Raphael
authors.initials: R
authors.lastname: Clynes
authors.affiliation: Department of Dermatology, Herbert Irving Pavilion, Columbia University, 161 Fort Washington Avenue, New York, NY, 10032, USA ; Department of Genetics and Development, Columbia University, 701 West 168th Street, New York, NY, 10032, USA.
authors.forename: Angela M
authors.initials: AM
authors.lastname: Christiano