T-cell cytokines differentially control human monocyte antimicrobial responses by regulating vitamin D metabolism

被引：171

作者：

Edfeldt, Kristina ^{[1
]}

Liu, Philip T. ^{[1
,2
]}

Chun, Rene ^{[2
]}

Fabri, Mario ^{[1
]}

Schenk, Mirjam ^{[1
]}

Wheelwright, Matthew ^{[3
]}

Keegan, Caroline ^{[3
]}

Krutzik, Stephan R. ^{[1
]}

Adams, John S. ^{[2
]}

Hewison, Martin ^{[2
]}

Modlin, Robert L. ^{[1
,3
]}

机构：

[1] Univ Calif Los Angeles, David Geffen Sch Med, Div Dermatol, Dept Med, Los Angeles, CA 90095 USA

[2] Univ Calif Los Angeles, David Geffen Sch Med, Orthopaed Hosp, Dept Orthopaed Surg, Los Angeles, CA 90095 USA

[3] Univ Calif Los Angeles, David Geffen Sch Med, Dept Microbiol Mol Genet & Immunol, Los Angeles, CA 90095 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2010年 / 107卷 / 52期

基金：

美国国家卫生研究院;

关键词：

innate immune response; interferon-gamma; interleukin-4; Mycobacterium tuberculosis; TOLL-LIKE RECEPTOR-2; MYCOBACTERIUM-TUBERCULOSIS; CUTTING EDGE; IFN-GAMMA; MICROBIAL LIPOPROTEINS; CATHELICIDIN; ACTIVATION; AUTOPHAGY; INTERLEUKIN-4; MACROPHAGES;

D O I：

10.1073/pnas.1011624108

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

We investigated the mechanisms by which T-cell cytokines are able to influence the Toll-like receptor (TLR)-induced, vitamin D-dependent antimicrobial pathway in human monocytes. T-cell cytokines differentially influenced TLR2/1-induced expression of the antimicrobial peptides cathelicidin and DEFB4, being up-regulated by IFN-gamma, down-regulated by IL-4, and unaffected by IL-17. The Th1 cytokine IFN-gamma up-regulated TLR2/1 induction of 25-hydroxyvitamin D-1 alpha-hydroxylase (i.e., CYP27B1), leading to enhanced bioconversion of 25-hydroxyvitamin D-3 (25D(3)) to its active metabolite 1,25D(3). In contrast, the Th2 cytokine IL-4, by itself and in combination with the TLR2/1 ligand, induced catabolism of 25D(3) to the inactive metabolite 24,25D(3), and was dependent on expression of vitamin D-24-hydroxylase (i.e., CYP24A1). Therefore, the ability of T-cell cytokines to differentially control monocyte vitamin D metabolism represents a mechanism by which cell-mediated immune responses can regulate innate immune mechanisms to defend against microbial pathogens.

引用

页码：22593 / 22598

页数：6

共 29 条

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