MHC class II–dependent basophil–CD4+ T cell interactions promote TH2 cytokine–dependent immunity

Perrigoue, Jacqueline; Saenz, Steven A.; Siracusa, Mark C.; Allenspach, Eric J.; Taylor, Betsy C.; Giacomin, Paul; Nair, Meera G.; Du, Yurong; Zaph, Colby; Rooijen, Nico van; Comeau, Michael R.; Pearce, Edward J.; Laufer, Terri M.; Artis, David

doi:10.1038/ni.1740

Cited by 548 publications

(657 citation statements)

References 58 publications

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“…We next sought to assess which cell populations are critical for antigen presentation in our model. We first showed that basophils (17)(18)(19)(20)(21)(22) are not required for Nod-driven Th2 differentiation (Fig. S2).…”

Section: Ligand Sensing In the Stromal Compartment Is Necessary Formentioning

confidence: 99%

Nucleotide oligomerization domain-containing proteins instruct T cell helper type 2 immunity through stromal activation

Magalhães¹,

Rubino

Travassos³

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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Although a number of studies have examined the development of T-helper cell type 2 (Th2) immunity in different settings, the mechanisms underlying the initiation of this arm of adaptive immunity are not well understood. We exploited the fact that immunization with antigen plus either nucleotide-binding oligomerization domain-containing proteins 1 (Nod1) or 2 (Nod2) agonists drives Th2 induction to understand how these pattern-recognition receptors mediate the development of systemic Th2 immune responses. Here, we show in bone-marrow chimeric mice that Nod1 and Nod2 expression within the stromal compartment is necessary for priming of effector CD4 + Th2 responses and specific IgG1 antibodies. In contrast, sensing of these ligands by dendritic cells was not sufficient to induce Th2 immunity, although these cells contribute to the response. Moreover, we determined that CD11c + cells were the critical antigen-presenting cells, whereas basophils and B cells did not affect the capacity of Nod ligands to induce CD4 + Th2 effector function. Finally, we found that full Th2 induction upon Nod1 and Nod2 activation was dependent on both thymic stromal lymphopoietin production by the stromal cells and the up-regulation of the costimulatory molecule, OX40 ligand, on dendritic cells. This study provides in vivo evidence of how systemic Th2 immunity is induced in the context of Nod stimulation. Such understanding will influence the rational design of therapeutics that could reprogram the immune system during an active Th1–mediated disease, such as Crohn's disease.

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Section: Ligand Sensing In the Stromal Compartment Is Necessary Formentioning

confidence: 99%

Nucleotide oligomerization domain-containing proteins instruct T cell helper type 2 immunity through stromal activation

Magalhães¹,

Rubino

Travassos³

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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“…Thus, even though the findings presented herein are based on a small dataset of heterogeneous tumor subtypes, and our results may be biased because of sample selection favoring large and/or less CTX-responsive tumors among the CTX-treated group, the clear distinctions in the myeloid profiles between CTX-naive and CTX-treated tumors is provocative and indicates that a CSF1-targeted strategy may be a promising approach to enhance therapeutic efficacy of cytotoxic CTX, particularly for treatment of refractory BC. Moreover, given the increase in granulocytic populations within tumors resistant to CTX, and the involvement of these cells in regulating immune responses in chronic inflammatory diseases (58)(59)(60)(61)(62), these populations may also be functionally relevant, and targeting common pathways of immune suppression within the tumor microenvironment may provide additional therapeutic opportunities to increase efficacy of neoadjuvant CTX. …”

Section: Discussionmentioning

confidence: 99%

Leukocyte composition of human breast cancer

Ruffell¹,

Rugo

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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Retrospective clinical studies have used immune-based biomarkers, alone or in combination, to predict survival outcomes for women with breast cancer (BC); however, the limitations inherent to immunohistochemical analyses prevent comprehensive descriptions of leukocytic infiltrates, as well as evaluation of the functional state of leukocytes in BC stroma. To more fully evaluate this complexity, and to gain insight into immune responses after chemotherapy (CTX), we prospectively evaluated tumor and nonadjacent normal breast tissue from women with BC, who either had or had not received neoadjuvant CTX before surgery. Tissues were evaluated by polychromatic flow cytometry in combination with confocal immunofluorescence and immunohistochemical analysis of tissue sections. These studies revealed that activated T lymphocytes predominate in tumor tissue, whereas myeloid lineage cells are more prominant in “normal” breast tissue. Notably, residual tumors from an unselected group of BC patients treated with neoadjuvant CTX contained increased percentages of infiltrating myeloid cells, accompanied by an increased CD8/CD4 T-cell ratio and higher numbers of granzyme B-expressing cells, compared with tumors removed from patients treated primarily by surgery alone. These data provide an initial evaluation of differences in the immune microenvironment of BC compared with nonadjacent normal tissue and reveal the degree to which CTX may alter the complexity and presence of selective subsets of immune cells in tumors previously treated in the neoadjuvant setting.

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“…127 For instance, dendritic cells in the skin of mice that are exposed to N. brasiliensis larvae or the contact sensitizer dibutyl phthalate (both of which induce type 2 immunity) acquire distinct transcriptional profiles, revealing a previously unappreciated role for type I interferons during parasite infection, 128 and highlighting the complicated nature of pathogen recognition by the innate immune system. Interestingly, some studies suggest that ILC, 129-131 basophils, [132][133][134] and eosinophils 135,136 can express major histocompatibility complex class II and directly prime Th2 responses, notably upon N. brasiliensis 131 and T. muris 132 infections, with each cell type having been shown to migrate to the mesenteric lymph nodes during infection. 85,87,137,138 However, given that protective immunity is abolished in mice where all 139,140 or specific subsets 104-106,108,109 of dendritic cells have been depleted, it is perhaps more likely that these other innate cells contribute to local tissue immunity by promoting dendritic cell activation, or by further enhancing the cytokine response of mature T cells that have migrated to the infected tissue.…”

Section: Inductionmentioning

confidence: 99%