Mucosal Immune Responses to Microbiota in the Development of Autoimmune Disease Kristine A. Kuhn, MD, PhD a , Isabel Pedraza, MD b , M. Kristen Demoruelle, MD a, * INTRODUCTION Humans live in symbiosis with greater than or equal to 10 14 microorganisms that reside on epithelial surfaces of the body, including the skin and mucosal surfaces of the respiratory, gastrointestinal (GI), and genitourinary (GU) tracts. 1 These microbiota can be pathogenic or nonpathogenic, and they include a diverse community of Disclosure: The authors declare no conflicts of interest. a Division of Rheumatology, University of Colorado School of Medicine, 13001 E. 17th Place, Aurora, CO 80045, USA; b Division of Pulmonary/Critical Care Medicine, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA 90048, USA * Corresponding author. Division of Rheumatology, University of Colorado School of Medicine, 1775 Aurora Court, Mail Stop B-115, Aurora, CO 80045. E-mail address: Kristen.Demoruelle@UCDenver.edu KEYWORDS  Microbiota  Pathogenesis  Mucosal immunity  Autoimmune disease KEY POINTS  Mucosal microbiota can generate autoimmunity through a variety of mechanisms, including molecular mimicry, alteration of host antigens, exposure of self-antigens, bystander activa- tion, modulation of immune reactivity, and breach of the mucosal firewall.  Autoimmune disease may be triggered by a single microorganism or alterations of the host microbial community.  Microbiota changes associated with autoimmune disease may represent causality or a change to the mucosal environment associated with systemic inflammation.  Prospective studies that evaluate microbial changes at each mucosal site during the pre- clinical period of autoimmunity are needed to better understand the influence of micro- organisms in the pathogenesis of autoimmune disease.  If specific microbiota are found causal or protective in the development of autoimmune disease, novel strategies can be developed that may ultimately prevent disease. Rheum Dis Clin N Am 40 (2014) 711–725 http://dx.doi.org/10.1016/j.rdc.2014.07.013 rheumatic.theclinics.com 0889-857X/14/$ – see front matter Ó 2014 Elsevier Inc. All rights reserved.