The EMBO Journal Peer Review Process File - EMBO-2014-89966 © European Molecular Biology Organization 1 Manuscript EMBO-2014-89966 Commensal microbiota influence systemic autoimmune responses Jens Van Praet, Erin Donovan, Inge Vanassche, Michael Drennan, Fien Windels, Amélie Dendooven, Liesbeth Allais, Claude Cuvelier, Fons van de Loo, Paula Norris, Andrey Kruglov, Sergei Nedospasov, Sylvie Rabot, Raul Tito, Jeroen Raes, Valerie Gaboriau-Routhiau, Nadine Cerf- Bensussan, Tom Van de Wiele, Gerard Eberl, Carl Ware and Dirk Elewaut Corresponding author: Dirk Elewaut, University Hospital Ghent Review timeline: Submission date: 24 February 2014 Editorial Decision: 19 March 2014 resubmission: 03 September 2014 Editorial Decision: 02 October 2014 Revision received: 12 November 2014 Accepted: 01 December 2014 Editor: Karin Dumstrei Transaction Report: (Note: With the exception of the correction of typographical or spelling errors that could be a source of ambiguity, letters and reports are not edited. The original formatting of letters and referee reports may not be reflected in this compilation.) 1st Editorial Decision 19 March 2014 Thank you for submitting your manuscript to The EMBO journal. Your manuscript has now been seen by the three referees and I am afraid that their recommendations are not very positive at this stage. The referees clearly find the analysis interesting. However they also raise similar issues with the paper and find that the link between commensal microbiota and anti-nuclear antibody responses is not sufficiently substantiated by the data presented. Given the raised concerns and as it is not trivial to address them, I unfortunately see no other option but to reject the present submission. I am very sorry that I can't be more positive at this stage. REFEREE REPORTS Referee #1: Van Praet et al report that the systemic immune responses specifically anti-nuclear antibody (ANA) responses are influenced by commensal microbiota. They showed that about ~25% of the lymphotoxin (LT) receptor β deficient mice spontaneously develop ANAs. Similarly blocking LT- signaling at late stages of development also resulted in spontaneous ANA production. Thymic