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 journalArticlepeer-review

10 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


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