Metabolic regulation of follicular helper T cell differentiation in a mouse model of lupus

Xueyang Zou, Seung Chul Choi, Leilani Zeumer-Spataro, Yogesh Scindia, Emily K. Moser, Laurence Morel

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Follicular helper T (TFH) cells are expanded in systemic lupus erythematosus (SLE), where they are required for production of high affinity autoantibodies. A better understanding of the mechanisms that regulate the differentiation of TFH cells is critical. Naïve T cells from lupus-prone B6.NZM2410.Sle1.Sle2.Sle3 (TC) mice showed an intrinsic higher capacity to differentiate into TFH cells. Metabolic reprogramming is a vital regulatory mechanism for T cell differentiation, but how metabolic pathways contribute to TFH cell expansion in SLE remains elusive. Here we show that glycolysis, mTOR signaling, FAO, and the activity of complex V of the electron transport chain support TFH lineage commitment. Blocking complex I uniquely decreased the expansion of TFH cells from lupus-prone mice, and inhibition of some pathways had a greater effect in lupus-prone than control TFH cells. However, blocking glutaminolysis, complex III and ADP/ATP translocase did not affect TFH cell expansion. Together, our results identified novel intrinsic metabolic requirements for TFH cell differentiation, and further defined the differential metabolic pathways that support the expansion of TFH cells in lupus-prone mice. Together, our data indicates the crucial but distinct roles for metabolic pathways in TFH cell differentiation and provide a comprehensive experimental basis for fully understanding the precise roles of distant metabolic signaling in regulating the TFH cell differentiation.

Original languageEnglish (US)
Pages (from-to)13-21
Number of pages9
JournalImmunology Letters
Volume247
DOIs
StatePublished - Jul 2022
Externally publishedYes

Keywords

  • Follicular helper T cells
  • Metabolic pathways
  • SLE

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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