Hematopoietic stem and multipotent progenitor cells produce IL-17, IL-21 and other cytokines in response to TLR signals associated with late apoptotic products and augment memory Th17 and Tc17 cells in the bone marrow of normal and lupus mice

Ching I. Chen, Li Zhang, Syamal K. Datta*

*Corresponding author for this work

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

We studied effects of early and late apoptotic (necroptotic) cell products, related damage associated alarmins and TLR agonists, on hematopoietic stem and progenitor cells (HSPC). Surprisingly, normal HSPC themselves produced IL-17 and IL-21 after 11/2days of stimulation, and the best stimulators were TLR 7/8 agonist; HMGB1-DNA; TLR 9 agonist, and necroptotic B cells. The stimulated HSPC expressed additional cytokines/mediators, directly causing rapid expansion of IL-17+ memory CD4 T (Th17), and CD8 T (Tc17) cells, and antigen-experienced IL-17+ T cells with "naïve" phenotype. In lupus marrow, HSPC were spontaneously pre-stimulated by endogenous signals to produce IL-17 and IL-21. In contrast to HSPC, megakaryocyte progenitors (MKP) did not produce IL-17, and unlike HSPC, they could process and present particulate apoptotic autoantigens to augment autoimmune memory Th17 response. Thus abnormally stimulated primitive hematopoietic progenitors augment expansion of IL-17 producing immune and autoimmune memory T cells in the bone marrow, which may affect central tolerance.

Original languageEnglish (US)
Pages (from-to)9-26
Number of pages18
JournalClinical Immunology
Volume162
DOIs
StatePublished - Jan 1 2016

Fingerprint

Th17 Cells
Interleukin-17
Hematopoietic Stem Cells
Stem Cells
Bone Marrow
Cytokines
interleukin-21
Central Tolerance
Megakaryocyte Progenitor Cells
HMGB1 Protein
CD8 Antigens
T-Lymphocytes
Viral Tumor Antigens
B-Lymphocytes

Keywords

  • Apoptosis
  • Bone marrow
  • Cytokines
  • Hematopoietic progenitors
  • Lupus
  • Memory Th17/Tc17 cells
  • TLR signals

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

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title = "Hematopoietic stem and multipotent progenitor cells produce IL-17, IL-21 and other cytokines in response to TLR signals associated with late apoptotic products and augment memory Th17 and Tc17 cells in the bone marrow of normal and lupus mice",
abstract = "We studied effects of early and late apoptotic (necroptotic) cell products, related damage associated alarmins and TLR agonists, on hematopoietic stem and progenitor cells (HSPC). Surprisingly, normal HSPC themselves produced IL-17 and IL-21 after 11/2days of stimulation, and the best stimulators were TLR 7/8 agonist; HMGB1-DNA; TLR 9 agonist, and necroptotic B cells. The stimulated HSPC expressed additional cytokines/mediators, directly causing rapid expansion of IL-17+ memory CD4 T (Th17), and CD8 T (Tc17) cells, and antigen-experienced IL-17+ T cells with {"}na{\"i}ve{"} phenotype. In lupus marrow, HSPC were spontaneously pre-stimulated by endogenous signals to produce IL-17 and IL-21. In contrast to HSPC, megakaryocyte progenitors (MKP) did not produce IL-17, and unlike HSPC, they could process and present particulate apoptotic autoantigens to augment autoimmune memory Th17 response. Thus abnormally stimulated primitive hematopoietic progenitors augment expansion of IL-17 producing immune and autoimmune memory T cells in the bone marrow, which may affect central tolerance.",
keywords = "Apoptosis, Bone marrow, Cytokines, Hematopoietic progenitors, Lupus, Memory Th17/Tc17 cells, TLR signals",
author = "Chen, {Ching I.} and Li Zhang and Datta, {Syamal K.}",
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T1 - Hematopoietic stem and multipotent progenitor cells produce IL-17, IL-21 and other cytokines in response to TLR signals associated with late apoptotic products and augment memory Th17 and Tc17 cells in the bone marrow of normal and lupus mice

AU - Chen, Ching I.

AU - Zhang, Li

AU - Datta, Syamal K.

PY - 2016/1/1

Y1 - 2016/1/1

N2 - We studied effects of early and late apoptotic (necroptotic) cell products, related damage associated alarmins and TLR agonists, on hematopoietic stem and progenitor cells (HSPC). Surprisingly, normal HSPC themselves produced IL-17 and IL-21 after 11/2days of stimulation, and the best stimulators were TLR 7/8 agonist; HMGB1-DNA; TLR 9 agonist, and necroptotic B cells. The stimulated HSPC expressed additional cytokines/mediators, directly causing rapid expansion of IL-17+ memory CD4 T (Th17), and CD8 T (Tc17) cells, and antigen-experienced IL-17+ T cells with "naïve" phenotype. In lupus marrow, HSPC were spontaneously pre-stimulated by endogenous signals to produce IL-17 and IL-21. In contrast to HSPC, megakaryocyte progenitors (MKP) did not produce IL-17, and unlike HSPC, they could process and present particulate apoptotic autoantigens to augment autoimmune memory Th17 response. Thus abnormally stimulated primitive hematopoietic progenitors augment expansion of IL-17 producing immune and autoimmune memory T cells in the bone marrow, which may affect central tolerance.

AB - We studied effects of early and late apoptotic (necroptotic) cell products, related damage associated alarmins and TLR agonists, on hematopoietic stem and progenitor cells (HSPC). Surprisingly, normal HSPC themselves produced IL-17 and IL-21 after 11/2days of stimulation, and the best stimulators were TLR 7/8 agonist; HMGB1-DNA; TLR 9 agonist, and necroptotic B cells. The stimulated HSPC expressed additional cytokines/mediators, directly causing rapid expansion of IL-17+ memory CD4 T (Th17), and CD8 T (Tc17) cells, and antigen-experienced IL-17+ T cells with "naïve" phenotype. In lupus marrow, HSPC were spontaneously pre-stimulated by endogenous signals to produce IL-17 and IL-21. In contrast to HSPC, megakaryocyte progenitors (MKP) did not produce IL-17, and unlike HSPC, they could process and present particulate apoptotic autoantigens to augment autoimmune memory Th17 response. Thus abnormally stimulated primitive hematopoietic progenitors augment expansion of IL-17 producing immune and autoimmune memory T cells in the bone marrow, which may affect central tolerance.

KW - Apoptosis

KW - Bone marrow

KW - Cytokines

KW - Hematopoietic progenitors

KW - Lupus

KW - Memory Th17/Tc17 cells

KW - TLR signals

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