Tlr4 regulates IFN-γ and IL-17 production by both thymic and induced Foxp3+Tregsduring intestinal inflammation

Anthony T. Cao, Suxia Yao, Andrew T. Stefka, Zhanju Liu, Hongwei Qin, Houpu Liu, Heather L. Evans-Marin, Charles O. Elson, Cathryn R. Nagler, Yingzi Cong

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Tregs play a crucial role in the maintenance of intestinal immune homeostasis. However, significant numbers of Foxp3+Tregs accumulate in the inflamed lesions in experimental colitis and in IBD patients. Tregproduction of the proinflammatory cytokines IFN-γ and/or IL-17 may arguably explain their ineffectiveness in suppressing intestinal inflammation. However, it remains unknown whether iTregand tTregproduce proinflammatory cytokines and how TLR signaling regulates this process. Here, we found that Foxp3+Tregswere increased in the intestines of B6.TLR4-/-and B6.IL-10-/-mice when compared with WT B6 mice. TLR4-/-and IL-10-/-resulted in more Tregswithin inflamed intestines. The majority of Foxp3+Tregsin the spleen was Helios-Nrp1-, whereas most Foxp3+Tregsin the intestinal LP were Helios+Nrp1+. More Helios-Nrp1-Tregsexpressed IFN-γand/or IL-17 than did Helios+Nrp1+Tregs in the spleen and intestine, which was increased with TLR4-/-. TLR4 signaling in T cells and APCs inhibited Foxp3+induction via MyD88-dependent, TRIF-independent pathways, which was negatively regulated by SOCS3. Collectively, these data demonstrate Helios+Nrp1+tTregsand Helios--Nrp1-iTregsproduce proinflammatory cytokines in the intestines during inflammation, which was regulated by TLR4 signaling.

Original languageEnglish (US)
Pages (from-to)895-905
Number of pages11
JournalJournal of Leukocyte Biology
Volume96
Issue number5
DOIs
StatePublished - Nov 1 2014

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Interleukin-17
Intestines
Inflammation
Cytokines
Interleukin-10
Spleen
Colitis
Homeostasis
Maintenance
T-Lymphocytes

Keywords

  • Colitis
  • LPS
  • MyD88
  • SOCS3

ASJC Scopus subject areas

  • Cell Biology
  • Immunology
  • Medicine(all)

Cite this

Tlr4 regulates IFN-γ and IL-17 production by both thymic and induced Foxp3+Tregsduring intestinal inflammation. / Cao, Anthony T.; Yao, Suxia; Stefka, Andrew T.; Liu, Zhanju; Qin, Hongwei; Liu, Houpu; Evans-Marin, Heather L.; Elson, Charles O.; Nagler, Cathryn R.; Cong, Yingzi.

In: Journal of Leukocyte Biology, Vol. 96, No. 5, 01.11.2014, p. 895-905.

Research output: Contribution to journalArticle

Cao, Anthony T. ; Yao, Suxia ; Stefka, Andrew T. ; Liu, Zhanju ; Qin, Hongwei ; Liu, Houpu ; Evans-Marin, Heather L. ; Elson, Charles O. ; Nagler, Cathryn R. ; Cong, Yingzi. / Tlr4 regulates IFN-γ and IL-17 production by both thymic and induced Foxp3+Tregsduring intestinal inflammation. In: Journal of Leukocyte Biology. 2014 ; Vol. 96, No. 5. pp. 895-905.
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AU - Liu, Zhanju

AU - Qin, Hongwei

AU - Liu, Houpu

AU - Evans-Marin, Heather L.

AU - Elson, Charles O.

AU - Nagler, Cathryn R.

AU - Cong, Yingzi

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