Interactions Between IL-17 Variants and Streptococcus in the Gut Contribute to the Development of Atopic Dermatitis in Infancy

Mi Jin Kang; So Yeon Lee; Yoon Mee Park; Bong Soo Kim; Min Jung Lee; Jeong Hyun Kim; Seonmi Jeong; Seung Hwa Lee; Min Jee Park; Eun Sang Rhee; Sungsu Jung; Jisun Yoon; Hyun Ju Cho; Eun Lee; Song I Yang; Dong In Suh; Kyung Won Kim; Youn Ho Sheen; Kangmo Ahn; Soo Jong Hong

doi:10.4168/aair.2021.13.3.404

Interactions Between IL-17 Variants and Streptococcus in the Gut Contribute to the Development of Atopic Dermatitis in Infancy

Allergy Asthma Immunol Res. 2021 May;13(3):404-419. doi: 10.4168/aair.2021.13.3.404.

Authors

Mi Jin Kang¹, So Yeon Lee², Yoon Mee Park³, Bong Soo Kim⁴, Min Jung Lee⁴, Jeong Hyun Kim⁵, Seonmi Jeong⁶, Seung Hwa Lee⁶, Min Jee Park², Eun Sang Rhee², Sungsu Jung⁷, Jisun Yoon⁸, Hyun Ju Cho⁹, Eun Lee¹⁰, Song I Yang¹¹, Dong In Suh¹², Kyung Won Kim¹³, Youn Ho Sheen¹⁴, Kangmo Ahn¹⁵, Soo Jong Hong¹⁶

Affiliations

¹ Humidifier Disinfectant Health Center, Asan Medical Center, Seoul, Korea.
² Department of Pediatrics, Childhood Asthma Atopy Center, Humidifier Disinfectant Health Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
³ Asan Institute for Life Science, Asan Medical Center, Seoul, Korea.
⁴ Department of Life Science, Multidisciplinary Genome Institute, Hallym University, Chuncheon, Korea.
⁵ Department of Medicine, University of Ulsan Collage of Medicine, Seoul, Korea.
⁶ Asan Institute for Life Science, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
⁷ Department of Pediatrics, Pusan National University Yangsan Hospital, Yangsan, Korea.
⁸ Department of Pediatrics, Mediplex Sejong Hospital, Incheon, Korea.
⁹ Department of Pediatrics, International St. Mary's Hospital, Catholic Kwandong University College of Medicine, Incheon, Korea.
¹⁰ Department of Pediatrics, Chonnam National University Hospital, Chonnam National University Medical School, Gwangju, Korea.
¹¹ Department of Pediatrics, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, Korea.
¹² Department of Pediatrics, Seoul National University College of Medicine, Seoul, Korea.
¹³ Department of Pediatrics, Yonsei University College of Medicine, Seoul, Korea.
¹⁴ Department of Pediatrics, CHA Gangnam Medical Center, CHA University College of Medicine, Seoul, Korea.
¹⁵ Department of Pediatrics, Environmental Health Center for Atopic Disease, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
¹⁶ Department of Pediatrics, Childhood Asthma Atopy Center, Humidifier Disinfectant Health Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. sjhong@amc.seoul.kr.

Abstract

Purpose: Interleukin (IL)-17 variants and perturbations in the gut microbiota may influence the development of atopic dermatitis (AD). However, unifying principles for variants of host and microbe interaction remains unclear. We sought to investigate whether IL-17 variants and gut microbiota affect the development of AD in infancy.

Methods: Composition of the gut microbiota was analyzed in fecal samples from 99 normal healthy and 61 AD infants at 6 months of age. The associations between total immunoglobulin E (IgE), the scoring atopic dermatitis (SCORAD), short-chain fatty acids, transcriptome and functional profile of the gut measured in these subjects and Streptococcus were analyzed. IL-6 and IL-8 in the human intestinal epithelial cell line (HIEC-6) were measured after stimulation of IL-17 and Streptococcus mitis.

Results: In this study, Streptococcus was enriched in infants with AD and was higher in those with the GA + AA of IL-17 (rs2275913) variant. Streptococcus was positively correlated with IgE and SCORAD in infants with AD and GA + AA of IL-17. Butyrate and valerate were negatively correlated with Streptococcus and were decreased in infants with AD and GA + AA. Bacterial genes for oxidative phosphorylation induced by reduced colonization of Clostridium were decreased compared with normal and GG. In transcriptome analysis, lactate dehydrogenase A-like 6B was higher in infants with AD compared with healthy infants. IL-6 and IL-8 were increased in IL-17 and/or S. mitis-stimulated HIEC-6 cells.

Conclusions: These findings suggest that increased Streptococcus and A allele of IL-17 (rs2275913) may contribute to the pathogenesis of AD via modulation of the immune system in infancy.

Keywords: Atopic dermatitis; IL-17; Streptococcus; gastrointestinal microbiome.

Abstract

Grants and funding