Ovalbumin-Induced Airway Inflammation Is Ameliorated in Dectin-1-Deficient Mice, in Which Pulmonary Regulatory T Cells Are Expanded through Modification of Intestinal Commensal Bacteria.

Wei Han, Ce Tang, Seiya Baba, Tomofumi Hamada, Tomoyuki Shimazu, Yoichiro Iwakura

Journal of immunology (Baltimore, Md. : 1950) 2021 May 01

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Asthma is an allergic chronic respiratory disease that affects more than 300 million people around the world. Dysbiosis of intestinal commensal microbiota influences the development of asthma. Dectin-1 (gene symbol: Clec7a), a C-type lectin receptor, plays an important role in the intestinal immune homeostasis by controlling regulatory T (Treg) cell differentiation through regulation of intestinal microbiota. However, it is not clear whether intestinal immune conditions affect immune responses in other organs. In this study, we examined the effects of Dectin-1 deficiency on allergic airway inflammation (AAI). OVA-induced AAI was attenuated in Clec7a -/- mice. Treg cells were more abundant in colonic lamina propria, mesenteric lymph nodes, and bronchoalveolar lavage fluid of Clec7a -/- mice after AAI induction. Treatment with antibiotics, but not an antifungal agent, decreased the abundance of intestinal Treg cells and aggravated the symptoms of AAI in Clec7a -/- mice. Transplantation of gut microbiota from Clec7a -/- mice into antibiotic-treated hosts increased the abundance of intestinal Treg cells and ameliorated AAI. Overcolonization by Lactobacillus murinus, a Dectin-1 signaling-regulated commensal bacterium, also promoted expansion of Treg cells in the colon and suppressed lung inflammation. Depletion of Treg cells with anti-CD25 Ab eliminated the phenotypic differences between wild-type and Clec7a -/- mice in OVA-induced AAI. These observations suggest that inhibition of Dectin-1 signaling ameliorates AAI by increasing the abundance of Treg cells in lungs through modification of intestinal commensal bacteria, suggesting a role for commensal microbiota in regulating inflammation in organs other than the intestine. Copyright © 2021 by The American Association of Immunologists, Inc.

Citation

Wei Han, Ce Tang, Seiya Baba, Tomofumi Hamada, Tomoyuki Shimazu, Yoichiro Iwakura. Ovalbumin-Induced Airway Inflammation Is Ameliorated in Dectin-1-Deficient Mice, in Which Pulmonary Regulatory T Cells Are Expanded through Modification of Intestinal Commensal Bacteria. Journal of immunology (Baltimore, Md. : 1950). 2021 May 01;206(9):1991-2000