Type 3 innate lymphoid cell-derived lymphotoxin prevents microbiota-dependent inflammation
- Authors
- Zhang, Yuan; Kim, Tae-Jin; Wroblewska, Joanna A.; Tesic, Vera; Upadhyay, Vaibhav; Weichselbaum, Ralph R.; Tumanov, Alexei V.; Tang, Hong; Guo, Xiaohuan; Tang, Haidong; Fu, Yang-Xin
- Issue Date
- 7월-2018
- Publisher
- CHIN SOCIETY IMMUNOLOGY
- Keywords
- germ-free; lymphotoxin; microbiota; splenomegaly; type 3 innate lymphoid cells
- Citation
- CELLULAR & MOLECULAR IMMUNOLOGY, v.15, no.7, pp.697 - 709
- Indexed
- SCIE
SCOPUS
- Journal Title
- CELLULAR & MOLECULAR IMMUNOLOGY
- Volume
- 15
- Number
- 7
- Start Page
- 697
- End Page
- 709
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/74422
- DOI
- 10.1038/cmi.2017.25
- ISSN
- 1672-7681
- Abstract
- Splenomegaly is a well-known phenomenon typically associated with inflammation. However, the underlying cause of this phenotype has not been well characterized. Furthermore, the splenomegaly phenotype seen in lymphotoxin (LT) signaling-deficient mice is characterized by increased numbers of splenocytes and splenic neutrophils. Splenomegaly, as well as the related phenotype of increased lymphocyte counts in non-lymphoid tissues, is thought to result from the absence of secondary lymphoid tissues in LT-deficient mice. We now present evidence that mice deficient in LT alpha(1)beta(2) or LT beta R develop splenomegaly and increased numbers of lymphocytes in non-lymphoid tissues in a microbiota-dependent manner. Antibiotic administration to LT alpha(1)beta(2)- or LT beta R-deficient mice reduces splenomegaly. Furthermore, re-derived germ-free Ltbr(-/- ) mice do not exhibit splenomegaly or increased inflammation in non-lymphoid tissues compared to specific pathogen-free Ltbr(-/- )mice. By using various LID- and LTM-conditional knockout mice, we demonstrate that retinoic acid-related orphan receptor gamma T-positive type 3 innate lymphoid cells provide the required active LT signaling to prevent the development of splenomegaly. Thus, this study demonstrates the importance of LT-mediated immune responses for the prevention of splenomegaly and systemic inflammation induced by microbiota.
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