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PMID: 20864093 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

Rap1A regulates generation of T regulatory cells via LFA-1-dependent and LFA-1-independent mechanisms.

Cellular immunology ·Vol. 266 ·No. 1 ·2010-00-00 ·Pages 7-13

Li L, Kim Js, Boussiotis VA

Abstract

The small GTPase Rap1A has a critical role in regulating cell-matrix and cell-cell adhesion. In T lymphocytes, Rap1A mediates LFA-1 activation and LFA-1-mediated adhesion. LFA-1 reduces the threshold of TCR signals for low affinity ligands. Previously, we determined that mice expressing constitutively active Rap1A on T cells have increased frequency of CD103(+) T regulatory cells (Treg). We hypothesized that Rap1A-GTP might affect the differentiation of Treg by regulating LFA-1 activation. Using Foxp3-GFP-KI, LFA-1-KO and Rap1A-GTP-Tg mice we determined that Rap1A has an active role in the development of thymic Treg but LFA-1 is not mandatory for this function. Rap1A is also involved in the generation of peripheral Treg and this effect is mediated via LFA-1-dependent and LFA-1-independent mechanisms. Identification of the signaling pathways via which Rap1-GTP contributes to the differentiation of Treg will provide new insights to the function of Rap1A and to designing targeted approaches for generation of Treg for therapeutic applications.

MeSH Terms
Adoptive Transfer Animals CD3 Complex/immunology CD4-Positive T-Lymphocytes/cytology,drug effects,immunology,metabolism CD8-Positive T-Lymphocytes/cytology,immunology,metabolism Cell Count Cell Differentiation/drug effects,immunology Cell Proliferation/drug effects DNA-Binding Proteins/genetics Forkhead Transcription Factors/genetics,metabolism Lymph Nodes/cytology,immunology Lymphocyte Activation/immunology Lymphocyte Function-Associated Antigen-1/genetics,metabolism Mice Mice, Inbred C57BL Mice, Knockout Mice, Transgenic Spleen/cytology,immunology T-Lymphocytes, Regulatory/cytology,immunology,metabolism Thymus Gland/cytology,immunology Transforming Growth Factor beta/pharmacology rap1 GTP-Binding Proteins/genetics,metabolism
Chemicals
CD3 Complex DNA-Binding Proteins Forkhead Transcription Factors Foxp3 protein, mouse Lymphocyte Function-Associated Antigen-1 Rag2 protein, mouse Transforming Growth Factor beta rap1 GTP-Binding Proteins
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Li Lequn
Department of Hematology-Oncology and Cancer Biology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Kim Jin sub
Boussiotis Vassiliki A
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Article Info
Journal
Cellular immunology
Abbr.
Cell Immunol
ISSN
1090-2163
DOI
10.1016/j.cellimm.2010.08.014
Published
2010-00-00
Epub
2010-00-22
Pages
7-13
Language
English
Region
Netherlands
NLM ID
1246405
PMCID
PMC2966523
Subset
IM
Grants
NCI NIH HHS · R01 CA104596 · United States
NIAID NIH HHS · R21 AI043552 · United States
NIAID NIH HHS · R01 AI043552 · United States
NIAID NIH HHS · R56 AI043552 · United States
NIAID NIH HHS · R21 AI043552-06 · United States
NIAID NIH HHS · AI43552 · United States
NHLBI NIH HHS · HL087870 · United States
NCI NIH HHS · R21 CA123855-02 · United States
NHLBI NIH HHS · R21 HL087970-02 · United States
NCI NIH HHS · R21 CA123855 · United States
NCI NIH HHS · CA104596 · United States
NCI NIH HHS · CA123855 · United States
External Links
PubMed source DOI: 10.1016/j.cellimm.2010.08.014 PMC Full Text View journal details
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