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CD5 Promotes IL-10 Production in Chronic Lymphocytic Leukemia B Cells through STAT3 and NFAT2 Activation
- Source :
- Journal of Immunology, Journal of Immunology, Publisher : Baltimore : Williams & Wilkins, c1950-. Latest Publisher : Bethesda, MD : American Association of Immunologists, 2011, 186 (8), pp.4835-44. ⟨10.4049/jimmunol.1003050⟩
- Publication Year :
- 2011
- Publisher :
- The American Association of Immunologists, 2011.
-
Abstract
- B lymphocytes from chronic lymphocytic leukemia (CLL) display some CD5 transcripts for CD5 containing the known exon 1 (E1A) and other CD5 transcripts containing the new exon 1 (E1B). These malignant B cells, as well as B cell lines transfected with cDNA for E1A-cd5 or with cDNA for E1B-cd5 produce IL-10, raising the possibility that CD5 participates in the secretion of IL-10. We identified transcription factors involved in this production in CD5+ B lymphocytes from CLL patients and in E1A-cd5–transfected or E1B-cd5–transfected Jok cells. STAT3 is activated via phosphorylation of serine 727 but also NFAT2 through its translocation into the nucleus. Chromatin immunoprecipitation experiments confirmed the role of STAT3 and allowed the discovery of a role for NFAT2 in IL-10 production. Both transcription factors bind not only to the enhancer of the Il-10 gene but also to the promoter of the Il-5 and Il-13 genes. Furthermore, transfection of B cell lines with E1A-cd5 or E1B-cd5 established that activation of STAT3 and NFAT2 is regulated by CD5. The same holds true for the production of IL-10, IL-5, and IL-13 and the expression of the receptors for these cytokines. This interpretation was confirmed by two experiments. In the first, downregulation of CD5 by small interfering RNAs lowered the production of IL-10. In the second experiment, transfection of the GFP-NFAT2 gene into B lymphocytes induced nuclear translocation of NFAT2 in CD5+ but not in CD5− B cells. Thus, CD5 expression is associated with NFAT2 activity (and mildly STAT3 activity), indicating that CD5 controls IL-10 secretion.
- Subjects :
- Male
MESH: Interleukin-13
MESH: Interleukin-10
viruses
Chronic lymphocytic leukemia
MESH: Antigens, CD5
Gene Expression
MESH: Aged, 80 and over
0302 clinical medicine
immune system diseases
MESH: Reverse Transcriptase Polymerase Chain Reaction
MESH: Child
hemic and lymphatic diseases
Gene expression
Serine
Immunology and Allergy
Phosphorylation
Child
MESH: Leukemia, Lymphocytic, Chronic, B-Cell
Cells, Cultured
Aged, 80 and over
MESH: Aged
B-Lymphocytes
0303 health sciences
Interleukin-13
MESH: Middle Aged
Reverse Transcriptase Polymerase Chain Reaction
MESH: Infant, Newborn
MESH: STAT3 Transcription Factor
hemic and immune systems
Hep G2 Cells
Transfection
Middle Aged
Interleukin-10
medicine.anatomical_structure
[SDV.IMM]Life Sciences [q-bio]/Immunology
Female
RNA Interference
MESH: Cells, Cultured
STAT3 Transcription Factor
MESH: Cell Line, Tumor
MESH: Gene Expression
Blotting, Western
MESH: RNA Interference
Immunology
MESH: NFATC Transcription Factors
MESH: Hep G2 Cells
chemical and pharmacologic phenomena
Biology
CD5 Antigens
03 medical and health sciences
Cell Line, Tumor
MESH: B-Lymphocytes
medicine
Humans
MESH: Blotting, Western
MESH: Serine
Enhancer
Transcription factor
B cell
Aged
030304 developmental biology
MESH: Humans
NFATC Transcription Factors
MESH: Phosphorylation
Infant, Newborn
MESH: Interleukin-5
medicine.disease
Leukemia, Lymphocytic, Chronic, B-Cell
Molecular biology
MESH: Male
Interleukin-5
CD5
MESH: Female
Chromatin immunoprecipitation
030215 immunology
Subjects
Details
- ISSN :
- 15506606 and 00221767
- Volume :
- 186
- Database :
- OpenAIRE
- Journal :
- The Journal of Immunology
- Accession number :
- edsair.doi.dedup.....760c41f872dbc3917c24b803d5281584