Jak3 negatively regulates dendritic-cell cytokine production and survival

Kunihiro Yamaoka, Booki Min, Yong Jie Zhou, William E. Paul, John J. O'Shea

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

Cytokines are critical in regulating the development and function of diverse cells. Janus kinase 3 (Jak3) is a tyrosine kinase expressed in hematopoietic cells that associates with the common gamma chain (γc) and is required for signaling for a family of cytokines including interleukin-2 (IL-2), IL-4, IL-7, IL-9, IL-15, and IL-21; deficiency of either Jak3 or γc results in severe combined immunodeficiency (SCID). While Jak3 is essential for lymphoid-cell development, the potential roles for Jak3 in regulating dendritic cells (DCs) were unclear. Herein, we show that although CD8+CD11c+ splenic DCs are absent in Jak3-/- mice, bone marrow-derived DCs developed normally in vitro from Jak3 -/- precursor cells. In fact, the survival of Jak3-/- DCs was enhanced, and they expressed lower levels of proapoptotic proteins. Jak3-/- DCs exhibited normal antigen uptake and up-regulation of costimulatory molecules. However, Jak3-/- DCs produced more IL-12 and IL-10 in response to Toll-like receptor ligands, which correlated with enhanced T helper 1 (Th1) differentiation in vivo. In summary, Jak3 is not essential for DC development but unexpectedly appears to be an important negative regulator. These results may be relevant clinically for patients with SCID who have undergone hematopoietic stem cell transplantation and for patients who might be treated with a Jak3 inhibitor.

Original languageEnglish
Pages (from-to)3227-3233
Number of pages7
JournalBlood
Volume106
Issue number9
DOIs
Publication statusPublished - 2005 Nov
Externally publishedYes

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Janus Kinase 3
Dendritic Cells
Cytokines
Survival
Severe Combined Immunodeficiency
Interleukin-9
Interleukin-15
Interleukin-7
Toll-Like Receptors
Hematopoietic Stem Cell Transplantation
Interleukin-12
Stem cells
Interleukin-4
Interleukin-10
Protein-Tyrosine Kinases
Interleukin-2

ASJC Scopus subject areas

  • Hematology

Cite this

Yamaoka, K., Min, B., Zhou, Y. J., Paul, W. E., & O'Shea, J. J. (2005). Jak3 negatively regulates dendritic-cell cytokine production and survival. Blood, 106(9), 3227-3233. https://doi.org/10.1182/blood-2005-02-0769

Jak3 negatively regulates dendritic-cell cytokine production and survival. / Yamaoka, Kunihiro; Min, Booki; Zhou, Yong Jie; Paul, William E.; O'Shea, John J.

In: Blood, Vol. 106, No. 9, 11.2005, p. 3227-3233.

Research output: Contribution to journalArticle

Yamaoka, K, Min, B, Zhou, YJ, Paul, WE & O'Shea, JJ 2005, 'Jak3 negatively regulates dendritic-cell cytokine production and survival', Blood, vol. 106, no. 9, pp. 3227-3233. https://doi.org/10.1182/blood-2005-02-0769
Yamaoka, Kunihiro ; Min, Booki ; Zhou, Yong Jie ; Paul, William E. ; O'Shea, John J. / Jak3 negatively regulates dendritic-cell cytokine production and survival. In: Blood. 2005 ; Vol. 106, No. 9. pp. 3227-3233.
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