IL-12 can alleviate Th17-mediated allergic lung inflammation through induction of pulmonary IL-10 expression

28Citations
Citations of this article
35Readers
Mendeley users who have this article in their library.

Abstract

Interleukin (IL)-12 has been shown to suppress T helper type 2 (Th2)-induced pathogenesis that is associated with allergic asthma, largely through interferon (IFN)-γ production. We have recently shown that in the absence of T-bet, the major regulator of IFN-γ expression, allergic lung inflammation is primarily associated with IL-17-associated recruitment of neutrophils into the pulmonary tract of mice. In the absence of T-bet, exogenous IL-12 was still able to suppress neutrophilic infiltration and to diminish levels of IL-17, IL-23, and IL-23R, as well as retinoic acid-related orphan receptorγt, the transcriptional regulator of the Th17 pathway. The same effects were observed in T-bet-/- IFN-γ-/- double knockout mice, showing an IFN-γ-independent effect of IL-12 in this model. IL-10 expression in the lungs of T-bet-deficient mice was significantly increased after IL-12 treatment, and inoculation of anti-IL-10R mAb completely reversed the ability of IL-12 to suppress histological inflammation, recruitment of inflammatory cell subsets into the lung, bronchiole hyperresponsiveness, and IL-17 production. We conclude that Th17-mediated allergic lung inflammation that becomes dominant in the absence of effective IFN-γ signaling can be effectively suppressed by IL-12 through an IL-10-dependent mechanism. © 2010 Society for Mucosal Immunology.

References Powered by Scopus

Control of regulatory T cell development by the transcription factor Foxp3

7198Citations
N/AReaders
Get full text

Reciprocal developmental pathways for the generation of pathogenic effector T<inf>H</inf>17 and regulatory T cells

5971Citations
N/AReaders
Get full text

The Orphan Nuclear Receptor RORγt Directs the Differentiation Program of Proinflammatory IL-17<sup>+</sup> T Helper Cells

4353Citations
N/AReaders
Get full text

Cited by Powered by Scopus

TRUCKs: The fourth generation of CARs

548Citations
N/AReaders
Get full text

IL-12 release by engineered T cells expressing chimeric antigen receptors can effectively muster an antigen-independent macrophage response on tumor cells that have shut down tumor antigen expression

446Citations
N/AReaders
Get full text

Of CARs and TRUCKs: Chimeric antigen receptor (CAR) T cells engineered with an inducible cytokine to modulate the tumor stroma

294Citations
N/AReaders
Get full text

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Cite

CITATION STYLE

APA

Durrant, D. M., & Metzger, D. W. (2010). IL-12 can alleviate Th17-mediated allergic lung inflammation through induction of pulmonary IL-10 expression. Mucosal Immunology, 3(3), 301–311. https://doi.org/10.1038/mi.2010.9

Readers over time

‘10‘11‘12‘13‘14‘15‘16‘17‘18‘19‘20‘21‘22‘23‘2402468

Readers' Seniority

Tooltip

PhD / Post grad / Masters / Doc 14

52%

Researcher 8

30%

Professor / Associate Prof. 5

19%

Readers' Discipline

Tooltip

Agricultural and Biological Sciences 11

44%

Medicine and Dentistry 5

20%

Biochemistry, Genetics and Molecular Bi... 5

20%

Immunology and Microbiology 4

16%

Save time finding and organizing research with Mendeley

Sign up for free
0