A Requirement of Protein Geranylgeranylation for Chemokine Receptor Signaling and Th17 Cell Function in an Animal Model of Multiple Sclerosis
Authors: Jia Geng
Ciana Walcott
Gianna Elena Hammer
John Zhou
Gregory Swan
Quanquan Ding
Eunchong Park
Hsin-I Huang
Donghai Wang
Junyi J Zhang
Journal: Frontiers in Immunology (2021)
Discipline: IMMUNOLOGY
Keywords: T cells; adaptive immune response; autoimmunity; lymphocyte migration; protein geranylgeranylation.
Affiliations: Division of Rheumatology and Immunology, Department of Medicine, Duke University School of Medicine, Durham, NC, United States., Department of Immunology, Duke University School of Medicine, Durham, NC, United States.

Abstract:  Precisely controlled lymphocyte migration is critically required for immune surveillance and successful immune responses. Lymphocyte migration is strictly regulated by chemokines and chemokine receptors. Here we show that protein geranylgeranylation, a form of post-translational protein lipid modification, is required for chemokine receptor-proximal signaling. Mature thymocytes deficient for protein geranylgeranylation are impaired for thymus egress. Circulating mature T cells lacking protein geranylgeranylation fail to home to secondary lymphoid organs or to transmigrate in response to chemokines in vitro. Mechanistically, protein geranylgeranylation modifies the γ-subunits of the heterotrimeric small GTPases that are essential for chemokine receptor signaling. In addition, protein geranylgeranylation also promotes the differentiation of IL-17-producing T helper cells while inhibiting the differentiation of Foxp3+ regulatory T cells. Finally, mice with T cell lineage-specific deficiency of protein geranylgeranylation are resistant to experimental autoimmune encephalomyelitis induction. This study elucidated a critical role of protein geranylgeranylation in regulating T lymphocyte migration and function. 

Retracted: No

PubPeer comments:
 Dear authors, There seem to be two duplicated FACS plots in Fig.2A: ![file] , 
 Thank you again for bring this issue to our attention. The first author and the corresponding author had inspected the data together and found that what you found is correct. There were duplicated graphs which was a mistake happened during copying flow cytometry graphs into SVG and into Adobe Illustrator. We have corrected the figure and have submitted a correction request to the journal of Frontiers in Immunology. Please let us know if you have any additional concerns. , 
 Thanks for the quick response and for correcting the dublication , 
 #2 In the paperu2019s methods, you state that the flow cytometry data was u201canalyzed using FlowJo,u201d and you explain above that the graphs were exported to SVG. How does this process explain the incorrect labels? , 
 #5 When we checked the SVG files in our original record, we found that the SVG was already incorrect. , 
 #4 We drag the individual graphs from flowjo into the layout of Flowjo and then export layout into SVG file. We then open the SVG file with AI to make it into the final figure by changing the size of the graphs and the fonts. The mistake happened with X dragging flow graphs into the layout within flow, he dragged the same graphs twice that led to duplication. The actual ones that should appear in the figure were not used instead. ,