RGD Reference Report - Interleukin 27R regulates CD4+ T cell phenotype and impacts protective immunity during Mycobacterium tuberculosis infection. - Rat Genome Database

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Interleukin 27R regulates CD4+ T cell phenotype and impacts protective immunity during Mycobacterium tuberculosis infection.

Authors: Torrado, E  Fountain, JJ  Liao, M  Tighe, M  Reiley, WW  Lai, RP  Meintjes, G  Pearl, JE  Chen, X  Zak, DE  Thompson, EG  Aderem, A  Ghilardi, N  Solache, A  McKinstry, KK  Strutt, TM  Wilkinson, RJ  Swain, SL  Cooper, AM 
Citation: Torrado E, etal., J Exp Med. 2015 Aug 24;212(9):1449-63. doi: 10.1084/jem.20141520. Epub 2015 Aug 17.
RGD ID: 11086047
Pubmed: PMID:26282876   (View Abstract at PubMed)
PMCID: PMC4548054   (View Article at PubMed Central)
DOI: DOI:10.1084/jem.20141520   (Journal Full-text)

CD4+ T cells mediate protection against Mycobacterium tuberculosis (Mtb); however, the phenotype of protective T cells is undefined, thereby confounding vaccination efforts. IL-27 is highly expressed during human tuberculosis (TB), and absence of IL-27R (Il27ra) specifically on T cells results in increased protection. IL-27R deficiency during chronic Mtb infection does not impact antigen-specific CD4+ T cell number but maintains programmed death-1 (PD-1), CD69, and CD127 expression while reducing T-bet and killer cell lectin-like receptor G1 (KLRG1) expression. Furthermore, T-bet haploinsufficiency results in failure to generate KLRG1+, antigen-specific CD4+ T cells, and in improved protection. T cells in Il27ra(-/-) mice accumulate preferentially in the lung parenchyma within close proximity to Mtb, and antigen-specific CD4+ T cells lacking IL-27R are intrinsically more fit than intact T cells and maintain IL-2 production. Improved fitness of IL-27R-deficient T cells is not associated with increased proliferation but with decreased expression of cell death-associated markers. Therefore, during Mtb infection, IL-27R acts intrinsically on T cells to limit protection and reduce fitness, whereas the IL-27R-deficient environment alters the phenotype and location of T cells. The significant expression of IL-27 in TB and the negative influence of IL-27R on T cell function demonstrate the pathway by which this cytokine/receptor pair is detrimental in TB.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
tuberculosis exacerbatesHEP 11086047mRNA:increased expression:blood (human)RGD 

Objects Annotated

Genes (Homo sapiens)
IL27  (interleukin 27)

Additional Information