Type 3 innate lymphoid cell-derived lymphotoxin prevents microbiota-dependent inflammation

Yuan Zhang, Tae Jin Kim, Joanna A. Wroblewska, Vera Tesic, Vaibhav Upadhyay, Ralph R. Weichselbaum, Alexei V Tumanov, Hong Tang, Xiaohuan Guo, Haidong Tang, Yang Xin Fu

Research output: Contribution to journalArticle

3 Scopus citations


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 LTα1β2 or LTβR develop splenomegaly and increased numbers of lymphocytes in non-lymphoid tissues in a microbiota-dependent manner. Antibiotic administration to LTα1β2- or LTβR-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 LTβ- and LTβR-conditional knockout mice, we demonstrate that retinoic acid-related orphan receptor γT-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.

Original languageEnglish (US)
Pages (from-to)697-709
Number of pages13
JournalCellular and Molecular Immunology
Issue number7
StatePublished - Jul 1 2018



  • germ-free
  • lymphotoxin
  • microbiota
  • splenomegaly
  • type 3 innate lymphoid cells

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Cite this

Zhang, Y., Kim, T. J., Wroblewska, J. A., Tesic, V., Upadhyay, V., Weichselbaum, R. R., Tumanov, A. V., Tang, H., Guo, X., Tang, H., & Fu, Y. X. (2018). Type 3 innate lymphoid cell-derived lymphotoxin prevents microbiota-dependent inflammation. Cellular and Molecular Immunology, 15(7), 697-709. https://doi.org/10.1038/cmi.2017.25