Open Access
CD5L/AIM Regulates Lipid Biosynthesis and Restrains Th17 Cell Pathogenicity
Chao Wang,Nir Yosef,Nir Yosef,Jellert T. Gaublomme,Jellert T. Gaublomme,Chuan Wu,Youjin Lee,Clary B. Clish,James Kaminski,Sheng Xiao,Gerd Meyer zu Hörste,Mathias Pawlak,Yasuhiro Kishi,Yasuhiro Kishi,Nicole Joller,Katarzyna Karwacz,Chen Zhu,Maria Ordovas-Montanes,Asaf Madi,Asaf Madi,Ivo Wortman,Toru Miyazaki,Raymond A. Sobel,Hongkun Park,Hongkun Park,Aviv Regev,Aviv Regev,Vijay K. Kuchroo,Vijay K. Kuchroo +28 more
TLDR
In this article, the authors used single-cell RNA-seq to identify CD5L/AIM as a regulator expressed in non-pathogenic, but not in pathogenic Th17 cells.Abstract:
Summary Th17 cells play a critical role in host defense against extracellular pathogens and tissue homeostasis but can induce autoimmunity. The mechanisms implicated in balancing "pathogenic" and "non-pathogenic" Th17 cell states remain largely unknown. We used single-cell RNA-seq to identify CD5L/AIM as a regulator expressed in non-pathogenic, but not in pathogenic Th17 cells. Although CD5L does not affect Th17 differentiation, it is a functional switch that regulates the pathogenicity of Th17 cells. Loss of CD5L converts non-pathogenic Th17 cells into pathogenic cells that induce autoimmunity. CD5L mediates this effect by modulating the intracellular lipidome, altering fatty acid composition and restricting cholesterol biosynthesis and, thus, ligand availability for Rorγt, the master transcription factor of Th17 cells. Our study identifies CD5L as a critical regulator of the Th17 cell functional state and highlights the importance of lipid metabolism in balancing immune protection and disease induced by T cells.read more
Citations
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References
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Journal ArticleDOI
Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells.
Estelle Bettelli,Yijun Carrier,Wenda Gao,Thomas Korn,Terry B. Strom,Mohamed Oukka,Howard L. Weiner,Vijay K. Kuchroo +7 more
TL;DR: It is shown that IL-6, an acute phase protein induced during inflammation, completely inhibits the generation of Foxp3+ Treg cells induced by TGF-β, and the data demonstrate a dichotomy in thegeneration of pathogenic (TH17) T cells that induce autoimmunity and regulatory (Foxp3+) T Cells that inhibit autoimmune tissue injury.
Journal ArticleDOI
IL-23 drives a pathogenic T cell population that induces autoimmune inflammation
Claire L. Langrish,Yi Yi Chen,Wendy M. Blumenschein,Jeanine D. Mattson,Beth Basham,Jonathan D. Sedgwick,Terrill K. McClanahan,Robert A. Kastelein,Daniel J. Cua +8 more
TL;DR: Using passive transfer studies, it is confirmed that these IL-23–dependent CD4+ T cells are highly pathogenic and essential for the establishment of organ-specific inflammation associated with central nervous system autoimmunity.
Journal ArticleDOI
Induction of Intestinal Th17 Cells by Segmented Filamentous Bacteria
Ivaylo I. Ivanov,Koji Atarashi,Nicolas Manel,Eoin L. Brodie,Tatsuichiro Shima,Ulas Karaoz,Dongguang Wei,Katherine C. Goldfarb,Clark A. Santee,Susan V. Lynch,Takeshi Tanoue,Akemi Imaoka,Kikuji Itoh,Kiyoshi Takeda,Yoshinori Umesaki,Kenya Honda,Dan R. Littman +16 more
TL;DR: The authors showed that colonisation of mice with a segmented filamentous bacterium (SFB) is sufficient to induce the appearance of CD4+ T helper cells that produce IL-17 and IL-22 (Th17 cells) in the lamina propria.
Journal ArticleDOI
TGFβ in the context of an inflammatory cytokine milieu supports de novo differentiation of IL-17-Producing T cells
Marc Veldhoen,Richard J. Hocking,Christopher J. Atkins,Richard M. Locksley,Brigitta Stockinger +4 more
TL;DR: The data indicate that, in the presence of IL-6, TGFbeta1 subverts Th1 and Th2 differentiation for the generation ofIL-17-producing T cells.
Journal ArticleDOI
Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation
Nicholas Arpaia,Clarissa Campbell,Xiying Fan,Stanislav Dikiy,Joris van der Veeken,Paul deRoos,Hui Liu,Justin R. Cross,Klaus Pfeffer,Paul J. Coffer,Alexander Y. Rudensky +10 more
TL;DR: The results suggest that bacterial metabolites mediate communication between the commensal microbiota and the immune system, affecting the balance between pro- and anti-inflammatory mechanisms.