Reciprocal Roles of Intestinal Microbiota in the Pathogenesis of Organ-Specific Autoimmune Diseases in a Lymphopenia-Induced Autoimmunity Mouse Model

Toshiki Eri¹, Kimito Kawahata², Ei Bannai¹, Takeyuki Kanzaki³, Lisa Akahira¹, Kazuya Michishita¹ and Kazuhiko Yamamoto¹, ¹Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan, ²Department of Rheumatology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo, Japan, ³Internal Medicine, Yamanashi Prefectural Central Hospital, Yamanashi, Japan

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: autoimmune diseases, lymphopenia, microbiome and mouse model, T cells

Session Information

Date: Monday, November 9, 2015

Title: Systemic Lupus Erythematosus - Animal Models Poster I

Session Type: ACR Poster Session B

Session Time: 9:00AM-11:00AM

Background/Purpose: Past studies reported lymphopenia mouse transfer model which transfer CD4⁺CD25^– cells from wild-type BALB/c mouse into athymic nude BALB/c mice produce lupus-like systemic autoantibodies and develop multiple organ-specific autoimmune diseases. Previously, we reported that transferred T cells undergo homeostatic proliferation and differentiate into follicular helper T cells under the presence of intestinal microbiota, which promote germinal center formation and autoantibody production within 4 weeks. Next, we would like to investigate the roles of intestinal microbiota in the pathogenesis of long-term organ-specific autoimmunity in this mouse model.

Methods: CD4⁺CD25^– cells taken from spleen of wild-type BALB/c mouse were adoptively injected into nude BALB/c mice. Some recipient mice were orally administrated broad-spectrum antibiotics including ciprofloxacin, imipenem, metronidazole and vancomycin in drinking water. Immunofluorescence, and ELISA were performed to detect ANAs and anti-parietal cell antibodies. Histopathological investigation was performed 5 month after the transfer.

Results: T cell-transferred nude mice developed gastritis, colitis, sialoadenitis and oophoritis at high rates in 5 months. Combination of above 4 antibiotics decreased the incidence of gastritis, colitis and oophoritis, but exacerbated sialoadenitis. Single vancomycin administration inhibited the colitis and exacerbated the others.

Conclusion: Depletion or alteration of intestinal microbiota can ameliorate or exacerbate organ-specific autoimmunity in a lymphopenia-induced autoimmunity mouse model. This result should be noted when we search for the novel microbiological therapeutic approach to autoimmune diseases. Further investigation is needed to detect specific microorganisms involved in the inflammation of each organ.

Disclosure: T. Eri, None; K. Kawahata, None; E. Bannai, None; T. Kanzaki, None; L. Akahira, None; K. Michishita, None; K. Yamamoto, None.

To cite this abstract in AMA style:

Eri T, Kawahata K, Bannai E, Kanzaki T, Akahira L, Michishita K, Yamamoto K. Reciprocal Roles of Intestinal Microbiota in the Pathogenesis of Organ-Specific Autoimmune Diseases in a Lymphopenia-Induced Autoimmunity Mouse Model [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/reciprocal-roles-of-intestinal-microbiota-in-the-pathogenesis-of-organ-specific-autoimmune-diseases-in-a-lymphopenia-induced-autoimmunity-mouse-model/. Accessed .

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