Epicutaneous antigen exposure induces a Th17 response that drives airway inflammation after inhalation challenge

He, Rui; Oyoshi, Michiko K.; Jin, Haoli; Geha, Raif S.

doi:10.1073/pnas.0706942104

Cited by 185 publications

(183 citation statements)

References 36 publications

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“…In the skin, both Th1 and Th2 cytokines have been reported following immunization with OVA and CT [24]. Our experiments are in agreement with a Th1 cytokine response following skin immunization [12,13] IL-17 expression by CD4 1 T cells was also observed following skin immunization with CT as has been reported using other strategies of immunization in the skin [13,14]. Recently, a dominant Th17 response was reported following intranasal immunization with OVA together with either CT or CTB [19].…”

Section: Discussionsupporting

confidence: 90%

“…Several strategies for skin immunization have been developed [10,12,14,24]. However, the nature of the CD4 1 T-cell response that is dominant in the skin and the role of migrating DCs in the presence of different adjuvants in shaping the immune response are important issues that need to be investigated.…”

Section: Discussionmentioning

confidence: 99%

“…Skin immunization has yielded controversial data, with some reports supporting a Th2-type response [10,11] and others a Th1-type response [12,13]. IL-17-producing CD4 1 T cells (Th17) have also been found after skin immunization [13,14]. …”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Intradermal immunization in the ear with cholera toxin and its non‐toxic β subunit promotes efficient Th1 and Th17 differentiation dependent on migrating DCs

et al. 2011

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The nature of CD4 1 T-cell responses after skin immunization and the role of migrating DCs in the presence of adjuvants in the elicited response are interesting issues to be investigated. Here, we evaluated the priming of CD4 1 T cells following ear immunization with low doses of model antigens in combination with either cholera toxin (CT) or the non-toxic b CT subunit (CTB) as an adjuvant. Following immunization with CT, we found efficient antigen presentation that is reflected in the production of IFN-c and IL-17 by CD4 1 T cells over IL-4 or IL-5 production. The CTB-induced activation of DCs in the ear occurred without visible inflammation, which reflects a similar type of CD4 1 T-cell differentiation. In both cases, the elicited response was dependent on the presence of migrating skin cells. Remarkably, immunization with CT or with CTB led to the induction of a delayed-type hypersensitivity (DTH) response in the ear. The DTH response that was induced by CT immunization was dependent on IL-17 and partially dependent on IFN-c activity. These results indicate that both CT and CTB induce an efficient CD4 1 T-cell response to a co-administered antigen following ear immunization that is dependent on migrating DCs.Key words: DCs . Migrating DCs . Skin immunization Supporting Information available online IntroductionThe skin is the first line of defense against microbial pathogens. There is supporting evidence that DCs are crucial for the initiation, polarization and control of the adaptive immune response [1,2]. Efficient immunosurveillance in the skin is based upon the continuous traffic of cells from the skin to the draining lymph nodes. Although Langerhans cells (LCs) have been shown to be potent APCs in vitro [3], in vivo approaches have produced conflicting data regarding their role in T-cell priming [4,5]. Dermal DCs are also migrating DCs that colonize lymph nodes more rapidly than LCs [6,7], and different roles for skin DC subsets in T-cell priming have been reported [7][8][9]. Skin immunization has yielded controversial data, with some reports supporting a Th2-type response [10,11] and others a Th1-type response [12,13]. IL-17-producing CD4 1 T cells (Th17) have also been found after skin immunization [13,14]. 2894Cholera toxin (CT) has a strong adjuvant effect [15]. When administered in the mucosa, CT can elicit a Th2-type response that is based on the production of IL-4, IL-5 and IL-10 but virtually no 17]. However, a mixed Th1/Th2 response that produces both IFN-g and IL-4 has also been observed [18], and the administration of ovalbumin (OVA) in combination with CT elicits a dominant Th17 response following intranasal immunization [19]. This dominance of IL-17 was also observed in response to the CT b subunit (CTB). Although the precise mechanism for the adjuvant effect of CT is not completely understood, it appears that CTB targets DCs in vivo by binding to the cell membrane ganglioside GM1 [20]; moreover, the CT a subunit (CTA) triggers the PKA-mediated induction of cAMP, which plays a critical role ...

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Intradermal immunization in the ear with cholera toxin and its non‐toxic β subunit promotes efficient Th1 and Th17 differentiation dependent on migrating DCs

et al. 2011

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“…In human donors suffering from Langerhans cell (LC) histiocytosis, IL-17A was found in skin LC, CD3/CD28-activated T cells, and monocyte-derived DC (MoDC), but not in MoDC from healthy donors [13]. Murine OVA-pulsed CD4 1 T cells secreted IL-17A after stimulation with skin-derived DC [14]. Considering a central role for IL-17 in the molecular processes of infectious diseases and autoimmunity, so far the Th17 driving factors remained obscure and species specific.…”

Section: Introductionmentioning

confidence: 99%

TLR2‐activated human langerhans cells promote Th17 polarization via IL‐1β, TGF‐β and IL‐23

et al. 2009

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“…Increased levels of IL-17 have been found in bronchoalveolar lavage fluid (BALF), sputum, and blood from patients with allergic asthma (15)(16)(17)(18)(19)(20). In mouse models of allergic asthma, systemic blockage of IL-17 inhibited the allergen-induced accumulation of neutrophils in the airway and AHR (20)(21)(22), suggesting that IL-17 plays an important role during the pathophysiological process of allergic asthma. Furthermore, Lajoie et al (23) have reported that not only severe AHR but also the increases in IL-17 production and IL-17 + CD4 + cells in asthmatic lungs were reduced in complement C3a receptor-deficient mice.…”

mentioning

confidence: 99%

Complement C3a-Induced IL-17 Plays a Critical Role in an IgE-Mediated Late-Phase Asthmatic Response and Airway Hyperresponsiveness via Neutrophilic Inflammation in Mice

Mizutani

Goshima

Nabe

et al. 2012

The Journal of Immunology

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Allergen-specific IgE plays an essential role in the pathogenesis of allergic asthma. Although there has been increasing evidence suggesting the involvement of IL-17 in the disease, the relationship between IL-17 and IgE-mediated asthmatic responses has not yet been defined. In this study, we attempted to elucidate the contribution of IL-17 to an IgE-mediated late-phase asthmatic response and airway hyperresponsiveness (AHR). BALB/c mice passively sensitized with an OVA-specific IgE mAb were challenged with OVA intratracheally four times. The fourth challenge caused a late-phase increase in airway resistance associated with elevated levels of IL-17+CD4+ cells in the lungs. Multiple treatments with a C3a receptor antagonist or anti-C3a mAb during the challenges inhibited the increase in IL-17+CD4+ cells. Meanwhile, a single treatment with the antagonist or the mAb at the fourth challenge suppressed the late-phase increase in airway resistance, AHR, and infiltration by neutrophils in bronchoalveolar lavage fluid. Because IL-17 production in the lungs was significantly repressed by both treatments, the effect of an anti–IL-17 mAb was examined. The late-phase increase in airway resistance, AHR, and infiltration by neutrophils in bronchoalveolar lavage fluid was inhibited. Furthermore, an anti–Gr-1 mAb had a similar effect. Collectively, we found that IgE mediated the increase of IL-17+CD4+ cells in the lungs caused by repeated Ag challenges via C3a. The mechanisms leading to the IgE-mediated late-phase asthmatic response and AHR are closely associated with neutrophilic inflammation through the production of IL-17 induced by C3a.

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Epicutaneous antigen exposure induces a Th17 response that drives airway inflammation after inhalation challenge

Cited by 185 publications

References 36 publications

Intradermal immunization in the ear with cholera toxin and its non‐toxic β subunit promotes efficient Th1 and Th17 differentiation dependent on migrating DCs

Intradermal immunization in the ear with cholera toxin and its non‐toxic β subunit promotes efficient Th1 and Th17 differentiation dependent on migrating DCs

TLR2‐activated human langerhans cells promote Th17 polarization via IL‐1β, TGF‐β and IL‐23

Complement C3a-Induced IL-17 Plays a Critical Role in an IgE-Mediated Late-Phase Asthmatic Response and Airway Hyperresponsiveness via Neutrophilic Inflammation in Mice

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