Gut-residing segmented filamentous bacteria drive autoimmune arthritis via T helper 17 cells

By Hsin-jung Wu, I. Ivanov, J. Darce, Kimie Hattori, T. Shima, Y. Umesaki, Dan R. Littman, C. Benoist, D. Mathis. Immunity, 2010

1,580 citations recorded by the source corpus.

SUMMARY Commensal microbes can have a substantial impact on autoimmune disorders, but the underlying molecular and cellular mechanisms remain largely unexplored. We report that autoimmune arthritis was strongly attenuated in the K/BxN mouse model under germ-free (GF) conditions, accompanied by reductions in serum autoantibody titers, splenic autoantibody-secreting cells, germinal centers and the splenic T helper 17 (Th17) cell population. Neutralization of interleukin-17 prevented arthritis development in specific-pathogen-free K/BxN mice due to a direct effect of this cytokine on B cells to inhibit germinal center formation. The systemic deficiencies of the GF animals reflected a loss of Th17 cells from the small intestinal lamina propria. Introduction of a single gut-residing species, segmented filamentous bacteria, into GF animals reinstated the lamina propria Th17 cell compartment and production of autoantibodies, and arthritis rapidly ensued. Thus, a single commensal microbe, via its ability to promote a specific Th-cell subset, can drive an autoimmune disease.

Subfields: Immunology

View Paper: https://www.semanticscholar.org/paper/05b3b69caeb8bd9da9ace7ca750a732eafb2bbc5

How researchers see this paper

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In Immunology

1. Y. Belkaid
2. Dan R. Littman
3. K. Honda
4. R. Flavell
5. Guido Kroemer
6. L. Zitvogel
7. D. Artis
8. D. Cua

Citations in the corpus

• The Microbiome in Infectious Disease and Inflammation (2012, positive): “Accumulating evidence suggests that a change in the gut microbiota composition has a key role not only in IBD, but also in the development of systemic immune diseases, such as rheumatoid arthritis (15, 16), encephalomyelitis (17, 18), type 1 diabetes (19, 20), and allergic diseases (21, 22).”
• The gut microbiome: Relationships with disease and opportunities for therapy (2018, background): “The observation that GF mice are protected from development of experimental arthritis (Wu et al., 2010) suggests a possible role for the microbiome in the pathogenesis of this disease.”
• The IL-17 family of cytokines in health and disease (2019, background): “, 2013), and have been demonstrated to contribute to arthritis susceptibility in mice (Maeda et al., 2016; Wu et al., 2010).”
• Immunoglobulin A coating identifies colitogenic bacteria in inflammatory bowel disease (2014, positive): “In addition, SFB is a potent driver of intestinal T helper 17 (Th17) cell responses in mice and has been shown to exacerbate development of arthritis (Ivanov et al., 2009; Wu et al., 2010).”
• Interaction between microbiota and immunity in health and disease (2020, background): “Similarly, inoculation of SFB into GF mice is sufficient to induce Th17 activation and to instigate autoimmune arthritis.(176) In addition to the enteric bacteria, the periodontal pathobiont Porphyromonas gingivalis can induce a TLR2- and IL-1-mediated Th17 response and thereby exacerbate autoimmune”
• Dysbiosis Contributes to Arthritis Development via Activation of Autoreactive T Cells in the Intestine (2016, methodology): “Among these models, germ-free IL-1Ra mice or germ-free K/BxN mice developed arthritis when monocolonized with L bifidus or SFB, respectively (11,12).”
• Role of the Microbiota in Immunity and inflammation (2014, background): “Arthritic phenotypes were completely restored when germ-free animals were monocolonized with SFB, which drives the differentiation and or dissemination of both intestinal and splenic Th17 cells (Wu et al., 2010).”
• The role of gut microbiota in immune homeostasis and autoimmunity (2012, methodology): “Recently, the K/BxN mouse, another spontaneous arthritis model, was used to provide a mechanism to explain the missing links among gut microbiota, systemic immunity and autoimmune arthritis.(16) At first, arthritis was shown to be reduced in K/BxN mice housed under GF conditions, which indicated a p”
• Expansion of intestinal Prevotella copri correlates with enhanced susceptibility to arthritis (2013, background): “Upon monocolonization of arthritis-prone K/BxN mice with SFB, the induced Th17 cells potentiate inflammatory disease (Wu et al., 2010).”