The Absence of Interleukin 1 Receptor–Related T1/St2 Does Not Affect T Helper Cell Type 2 Development and Its Effector Function

Abstract

T1/ST2, an orphan receptor with homology with the interleukin (IL)-1 receptor family, is expressed constitutively and stably on the surface of T helper type 2 (Th2) cells, but not on Th1 cells. T1/ST2 is also expressed on mast cells, which are critical for Th2-mediated effector responses. To evaluate whether T1/ST2 is required for Th2 responses and mast cell function, we have generated T1/ST2-deficient (T1/ST2−/−) mice and examined the roles of T1/ST2. Naive CD4+ T cells isolated from T1/ST2−/− mice developed to Th2 cells in response to IL-4 in vitro. T1/ST2−/− mice showed normal Th2 responses after infection with the helminthic parasite Nippostrongylus brasiliensis as well as in the mouse model of allergen-induced airway inflammation. In addition, differentiation and function of bone marrow–derived cultured mast cells were unaffected. These findings demonstrate that T1/ST2 does not play an essential role in development and function of Th2 cells and mast cells.

IL‐33‐activated dendritic cells are critical for allergic airway inflammation

“…This observation contrasts with those of Kurowska et al which showed that absence of IL-33 signalling does not affect IL-4 production [5,38]. This discrepancy can be explained by the difference in the asthma protocols or the doses of antigen administered during immunization [38][39][40]. Our model, using two sensitizations with low dose of OVA (10 mg/mouse) without adjuvant, followed by three OVA challenges (10 mg/mouse), seems to favour the development of classical Th2 cells that produce IL-4, IL-5 and IL-13, since we showed a reduction of all these cytokines in ST2-deficient mice.…”

“…Interestingly, we observed that cells from mLNs of ST2-deficient mice produced less Th2 cytokines, IL-4, IL-5 and IL-13 after antigen in vitro restimulation than cells isolated from WT mice. This observation contrasts with those of Kurowska et al which showed that absence of IL-33 signalling does not affect IL-4 production [5,38]. This discrepancy can be explained by the difference in the asthma protocols or the doses of antigen administered during immunization [38][39][40].…”

IL‐33 receptor (T1/ST2) signalling is necessary to prevent the development of encephalitis in mice infected with Toxoplasma gondii

“…These results are of particular significance as studies utilising T1/ST2 À/À mice have thus far failed to demonstrate, in a number of infectious disease models, that absence of the molecule can significantly increase rates of morbidity or mortality although these reports do provide evidence of alterations in the immune response [15,16]. Consequently, given our data and a previous During T. gondii infection the parasite preferentially forms cysts in tissues of the CNS that persist for the lifetime of the host [17].…”

“…These results are of particular significance as studies utilising T1/ST2 À/À mice have thus far failed to demonstrate, in a number of infectious disease models, that absence of the molecule can significantly increase rates of morbidity or mortality although these reports do provide evidence of alterations in the immune response [15,16]. Consequently, given our data and a previous report which demonstrated particularly high levels of IL-33 expression in the brain in comparison with other organs [12], the immune modulatory role of IL-33 receptor (IL-33R) signalling may have more relevance to the brain than other tissues.…”

“…The pathology witnessed in the brains of T1/ST2 À/À mice was related to increased parasite burden and a rise in the intracerebral expression of IFN-g, iNOS and TNF-a compared with their WT counterparts. Conversely, no significant pathological differences were identified in other tissues distinct from the brain between T1/ST2 À/À and WT BALB/c mice infected with T. gondii nor was there evidence of alterations in the systemic immune response as measured by levels of serum cytokines and antigen specific IgG1 or IgG2a antibodies.These results are of particular significance as studies utilising T1/ST2 À/À mice have thus far failed to demonstrate, in a number of infectious disease models, that absence of the molecule can significantly increase rates of morbidity or mortality although these reports do provide evidence of alterations in the immune response [15,16]. Consequently, given our data and a previous During T. gondii infection the parasite preferentially forms cysts in tissues of the CNS that persist for the lifetime of the host [17].…”