RGD Reference Report - IL-23 compensates for the absence of IL-12p70 and is essential for the IL-17 response during tuberculosis but is dispensable for protection and antigen-specific IFN-gamma responses if IL-12p70 is available.

General

IL-23 compensates for the absence of IL-12p70 and is essential for the IL-17 response during tuberculosis but is dispensable for protection and antigen-specific IFN-gamma responses if IL-12p70 is available.
Authors:	Khader, Shabaana A Pearl, John E Sakamoto, Kaori Gilmartin, Leigh Bell, Guy K Jelley-Gibbs, Dawn M Ghilardi, Nico deSauvage, Fred Cooper, Andrea M
Citation:	Khader SA, etal., J Immunol. 2005 Jul 15;175(2):788-95. doi: 10.4049/jimmunol.175.2.788.
RGD ID:	39457949
Pubmed:	PMID:16002675 (View Abstract at PubMed)
DOI:	DOI:10.4049/jimmunol.175.2.788 (Journal Full-text)
IL-12p70 induced IFN-gamma is required to control Mycobacterium tuberculosis growth; however, in the absence of IL-12p70, an IL-12p40-dependent pathway mediates induction of IFN-gamma and initial bacteriostatic activity. IL-23 is an IL-12p40-dependent cytokine containing an IL-12p40 subunit covalently bound to a p19 subunit that is implicated in the induction of CD4 T cells associated with autoimmunity and inflammation. We show that in IL-23 p19-deficient mice, mycobacterial growth is controlled, and there is no diminution in either the number of IFN-gamma-producing Ag-specific CD4 T cells or local IFN-gamma mRNA expression. Conversely, there is an almost total loss of both IL-17-producing Ag-specific CD4 T cells and local production of IL-17 mRNA in these mice. The absence of IL-17 does not alter expression of the antimycobacterial genes, NO synthase 2 and LRG-47, and the absence of IL-23 or IL-17, both of which are implicated in mediating inflammation, fails to substantially affect the granulomatous response to M. tuberculosis infection of the lung. Despite this redundancy, IL-23 is required to provide a moderate level of protection in the absence of IL-12p70, and this protection correlates with a requirement for IL-23 in the IL-12p70-independent induction of Ag-specific, IFN-gamma-producing CD4 T cells. We also show that IL-23 is required for the induction of an IL-17-producing Ag-specific phenotype in naive CD4 T cells in vitro and that absence of IL-12p70 promotes an increase in the number of IL-17-producing Ag-specific CD4 T cells both in vitro and in vivo.

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Term	Qualifier	Evidence	With	Reference	Notes	Source	Original Reference(s)
pulmonary tuberculosis		ISO	Il23a (Mus musculus)	39457949; 39457949		RGD
pulmonary tuberculosis		IMP		39457949		RGD

Objects Annotated

Genes (Rattus norvegicus)

Il23a (interleukin 23 subunit alpha)

Genes (Mus musculus)

Il23a (interleukin 23, alpha subunit p19)

Genes (Homo sapiens)

IL23A (interleukin 23 subunit alpha)

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IL-23 compensates for the absence of IL-12p70 and is essential for the IL-17 response during tuberculosis but is dispensable for protection and antigen-specific IFN-gamma responses if IL-12p70 is available.