IL-4Rα-responsive smooth muscle cells contribute to initiation of TH2 immunity and pulmonary pathology in Nippostrongylus brasiliensis infections

Horsnell, William; Vira, Alykhan; Kirstein, Frank; Mearns, Helen; Hoving, J. Claire; Cutler, Antony J.; Dewals, Benjamin G; Myburgh, Elmarie; Kimberg, Matti; Arendse, Berenice; White, Neil W.; Lopata, Andreas L.; Burger, Patricia E.; Brombacher, Frank

doi:10.1038/mi.2010.46

Cited by 29 publications

(28 citation statements)

References 54 publications

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“…This along with B cell-dependent induction of IL-13 production by endogenous CD4 + T cell and B cells would provide an important source of IL-13 to activate potential effector cell populations, including epithelial [13], [43], smooth muscle [12], [44] and innate immune cells [24], [45], [46].…”

Section: Discussionmentioning

confidence: 99%

IL-4Rα-Associated Antigen Processing by B Cells Promotes Immunity in Nippostrongylus brasiliensis Infection

et al. 2013

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In this study, B cell function in protective TH2 immunity against N. brasiliensis infection was investigated. Protection against secondary infection depended on IL-4Rα and IL-13; but not IL-4. Protection did not associate with parasite specific antibody responses. Re-infection of B cell-specific IL-4Rα−/− mice resulted in increased worm burdens compared to control mice, despite their equivalent capacity to control primary infection. Impaired protection correlated with reduced lymphocyte IL-13 production and B cell MHC class II and CD86 surface expression. Adoptive transfer of in vivo N. brasiliensis primed IL-4Rα expressing B cells into naïve BALB/c mice, but not IL-4Rα or IL-13 deficient B cells, conferred protection against primary N. brasiliensis infection. This protection required MHC class II compatibility on B cells suggesting cognate interactions by B cells with CD4+ T cells were important to co-ordinate immunity. Furthermore, the rapid nature of these protective effects by B cells suggested non-BCR mediated mechanisms, such as via Toll Like Receptors, was involved, and this was supported by transfer experiments using antigen pulsed Myd88−/− B cells. These data suggest TLR dependent antigen processing by IL-4Rα-responsive B cells producing IL-13 contribute significantly to CD4+ T cell-mediated protective immunity against N. brasiliensis infection.

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Section: Discussionmentioning

confidence: 99%

IL-4Rα-Associated Antigen Processing by B Cells Promotes Immunity in Nippostrongylus brasiliensis Infection

et al. 2013

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“…For instance, expression of the IL-4 receptor alpha, which is required for both IL-4 and IL-13 signalling is not required on smooth muscle cells for the development of experimental allergic asthma [66]. On the other hand, signalling through IL-4Rα contributes to initiation of Th2 immunity and pulmonary pathology during Nippostrongylus brasiliensis infections [67]. It also confers resistance during acute Schistosomiasis [68].…”

Section: Discussionmentioning

confidence: 99%

Helios Is Associated with CD4 T Cells Differentiating to T Helper 2 and Follicular Helper T Cells In Vivo Independently of Foxp3 Expression

et al. 2011

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BackgroundAlthough in vitro IL-4 directs CD4 T cells to produce T helper 2 (Th2)-cytokines, these cytokines can be induced in vivo in the absence of IL-4-signalling. Thus, mechanism(s), different from the in vitro pathway for Th2-induction, contribute to in vivo Th2-differentiation. The pathway for in vivo IL-4-independent Th2-differentiation has yet to be characterized.FindingsHelios (ikzf2), a member of the Ikaros transcription regulator family, is expressed in thymocytes and some antigen-matured T cells as well as in regulatory T cells. It has been proposed that Helios is a specific marker for thymus-derived regulatory T cells. Here, we show that mouse ovalbumin-specific CD4 (OTII) cells responding to alum-precipitated ovalbumin (alumOVA) upregulate Th2 features - GATA-3 and IL-4 - as well as Helios mRNA and protein. Helios is also upregulated in follicular helper T (TFh) cells in this response. By contrast, OTII cells responding to the Th1 antigen - live attenuated ovalbumin-expressing Salmonella - upregulate Th1 features - T-bet and IFN-γ - but not Helios. In addition, CD4 T cells induced to produce Th2 cytokines in vitro do not express Helios. The kinetics of Helios mRNA and protein induction mirrors that of GATA-3. The induction of IL-4, IL-13 and CXCR5 by alumOVA requires NF-κB1 and this is also needed for Helios upregulation. Importantly, Helios is induced in Th2 and TFh cells without parallel upregulation of Foxp3. These findings suggested a key role for Helios in Th2 and TFh development in response to alum-protein vaccines. We tested this possibility using Helios-deficient OTII cells and found this deficiency had no discernable impact on Th2 and TFh differentiation in response to alumOVA.ConclusionsHelios is selectively upregulated in CD4 T cells during Th2 and TFh responses to alum-protein vaccines in vivo, but the functional significance of this upregulation remains uncertain.

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“…Likewise, the increase in epithelial permeability during H. polygyrus infection, increasing fluid transfer, is STAT-6-dependent [43]. Furthermore, IL-4Rα-mediated signalling activates smooth muscle cells, leading to hypercontractibility during infection, while also stimulating Th2-promoting cytokine production from muscle cells [44]. …”

Section: A 3d View Of Anti-helminth Immunity: Disable Degrade and DImentioning

confidence: 99%

Susceptibility and immunity to helminth parasites

Maizels

Hewitson

Smith

2012

Current Opinion in Immunology

183

157

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IL-4Rα-responsive smooth muscle cells contribute to initiation of TH2 immunity and pulmonary pathology in Nippostrongylus brasiliensis infections

Cited by 29 publications

References 54 publications

IL-4Rα-Associated Antigen Processing by B Cells Promotes Immunity in Nippostrongylus brasiliensis Infection

IL-4Rα-Associated Antigen Processing by B Cells Promotes Immunity in Nippostrongylus brasiliensis Infection

Helios Is Associated with CD4 T Cells Differentiating to T Helper 2 and Follicular Helper T Cells In Vivo Independently of Foxp3 Expression

Susceptibility and immunity to helminth parasites

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