RGD Reference Report - T1/ST2 expression on Th2 cells negatively regulates allergic pulmonary inflammation. - Rat Genome Database

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T1/ST2 expression on Th2 cells negatively regulates allergic pulmonary inflammation.

Authors: Mangan, NE  Dasvarma, A  McKenzie, AN  Fallon, PG 
Citation: Mangan NE, etal., Eur J Immunol. 2007 May;37(5):1302-12.
RGD ID: 5144245
Pubmed: PMID:17407196   (View Abstract at PubMed)
DOI: DOI:10.1002/eji.200636520   (Journal Full-text)

The transmembrane form of T1/ST2 (ST2) is a specific marker on murine Th2 cells that have been generated in vitro, or isolated from sites of allergic type 2 inflammation. Despite the association of ST2 with Th2 cells, to date no obligate role for ST2 in type 2 responses in vivo has been described. We have specifically addressed the role of ST2 on T cells by generation of ST2(-/-) mice crossed with ovalbumin (OVA) T cell receptor-transgenic mice. OVA-specific ST2(-/-) cells had normal cytokine responses to T cell activation after in vitro Th2 differentiation, but OVA stimulation of IL-5 was increased. Transfer of OVA-specific ST2(-/-) Th2 cells into BALB/c mice caused exacerbated pulmonary inflammation with occluded airways, elevated airway hyper-responsiveness and increased susceptibility to methacholine challenge that was associated with mortalities of recipient mice. The increased pulmonary inflammation in OVA-specific ST2(-/-) Th2 cell recipients was associated with selective differences in pulmonary levels of Th2 cytokines compared with OVA-specific ST2(+) Th2 cell recipients. Recipients of OVA-specific ST2(-/-) Th2 cells had a significant increase in eosinophils and a significant reduction in F4/80(hi) macrophages in the lungs. This is the first demonstration of a role for ST2 expression on Th2 cells down-regulating pulmonary inflammation. These data have major implications for the targeting of ST2 as a therapy for allergic airway disorders.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
asthma  ISOIl1rl1 (Mus musculus)5144245; 5144245 RGD 
asthma  IMP 5144245 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Il1rl1  (interleukin 1 receptor-like 1)

Genes (Mus musculus)
Il1rl1  (interleukin 1 receptor-like 1)

Genes (Homo sapiens)
IL1RL1  (interleukin 1 receptor like 1)


Additional Information