Oral Administration Of Antigen Research Articles

Undenatured type II collagen protects against collagen-induced arthritis by restoring gut-joint homeostasis and immunity

Oral administration of harmless antigens can induce suppression of reactive immune responses, a process that capitalises on the ability of the gastrointestinal tract to tolerate exposure to food and commensal microbiome without triggering inflammatory responses. Repeating exposure to type II collagen induces oral tolerance and inhibits induction of arthritis, a chronic inflammatory joint condition. Although some mechanisms underlying oral tolerance are described, how dysregulation of gut immune networks impacts on inflammation of distant tissues like the joints is unclear. We used undenatured type II collagen in a prophylactic regime -7.33 mg/kg three times/week- to describe the mechanisms associated with protective oral immune-therapy (OIT) in gut and joint during experimental Collagen-Induced Arthritis (CIA). OIT reduced disease incidence to 50%, with reduced expression of IL-17 and IL-22 in the joints of asymptomatic mice. Moreover, whilst the gut tissue of arthritic mice shows substantial damage and activation of tissue-specific immune networks, oral administration of undenatured type II collagen protects against gut pathology in all mice, symptomatic and asymptomatic, rewiring IL-17/IL-22 networks. Furthermore, gut fucosylation and microbiome composition were also modulated. These results corroborate the relevance of the gut-joint axis in arthritis, showing novel regulatory mechanisms linked to therapeutic OIT in joint disease.

Oral administration of ovalbumin ameliorates specific food allergy via inhibiting gasdermin C-mediated pyroptosis and regulating microbial homeostasis

Early intervention with food allergenic proteins is considered the most promising and effective approach in preventing the onset of food allergy (FA). However, the effects of oral administration of protein antigens from different food sources on specific FA outcomes and its regulatory mechanisms remain largely unclear. Here, the Balb/c mice were treated with 5 mg of egg ovalbumin (OVA) or cow's milk β-lactoglobulin (BLG) for 5 days prior to intraperitoneal sensitization with OVA/Alum and oral challenge with 20 mg OVA. The results indicated that oral administration of both OVA and BLG significantly increased the proportion of regulatory T cells. However, the introduction of OVA, but not the bystander antigen BLG, prevented the occurrence of allergic diarrhea (OT-OVA group: 0% vs OT-BLG group: 100%) and mitigated the decrease in body temperature (OT-OVA group: 0.11 °C vs OT-BLG group: 1.1 °C). Specifically, the levels of serum immunoglobulin-E and mast cell protease-1 were significantly reduced, and the expression of zonula occludens-1, occludin, and claudin-1 was increased in the OVA-treated mice but not BLG-treated mice. Subsequently, transcriptome sequencing and Western blot analysis revealed that oral administration of OVA reduced the expression and cleavage of gasdermin C, which further decreased interleukin-33 secretion. Additionally, the dysregulation of the gut microbiota and short-chain fatty acid metabolism in the intestinal microenvironment caused by FA was reversed in OVA-treated mice but not BLG. In summary, our results presented a unique approach to ameliorate FA through targeting gasdermin C-mediated pyroptosis and dysbiosis of the gut microbiota in the intestinal microenvironment with OVA.

Oral Administration of Antigen Prevents Allergic Sensitization through Skin and Airways by Suppressing T Follicular Helper Cell Development

Oral Administration of Antigen Prevents Allergic Sensitization through Skin and Airways by Suppressing T Follicular Helper Cell Development

Distinct functions and transcriptional signatures in orally induced regulatory T cell populations

Oral administration of antigen induces regulatory T cells (Treg) that can not only control local immune responses in the small intestine, but also traffic to the central immune system to deliver systemic suppression. Employing murine models of the inherited bleeding disorder hemophilia, we find that oral antigen administration induces three CD4+ Treg subsets, namely FoxP3+LAP-, FoxP3+LAP+, and FoxP3-LAP+. These T cells act in concert to suppress systemic antibody production induced by therapeutic protein administration. Whilst both FoxP3+LAP+ and FoxP3-LAP+ CD4+ T cells express membrane-bound TGF-β (latency associated peptide, LAP), phenotypic, functional, and single cell transcriptomic analyses reveal distinct characteristics in the two subsets. As judged by an increase in IL-2Rα and TCR signaling, elevated expression of co-inhibitory receptor molecules and upregulation of the TGFβ and IL-10 signaling pathways, FoxP3+LAP+ cells are an activated form of FoxP3+LAP- Treg. Whereas FoxP3-LAP+ cells express low levels of genes involved in TCR signaling or co-stimulation, engagement of the AP-1 complex members Jun/Fos and Atf3 is most prominent, consistent with potent IL-10 production. Single cell transcriptomic analysis further reveals that engagement of the Jun/Fos transcription factors is requisite for mediating TGFβ expression. This can occur via an Il2ra dependent or independent process in FoxP3+LAP+ or FoxP3-LAP+ cells respectively. Surprisingly, both FoxP3+LAP+ and FoxP3-LAP+ cells potently suppress and induce FoxP3 expression in CD4+ conventional T cells. In this process, FoxP3-LAP+ cells may themselves convert to FoxP3+ Treg. We conclude that orally induced suppression is dependent on multiple regulatory cell types with complementary and interconnected roles.

Oral administration of ovalbumin protects mice from concanavalin A-induced hepatitis through suppression of interferon-gamma responses

The liver is a tolerogenic organ that exhibits hypo-responsiveness to antigens circulating in the portal vein. Antigens that are orally administered at high doses reach the liver. In our previous study, we demonstrated that administering ovalbumin (OVA) orally at high doses generates unique CD4+ T cells and tolerogenic dendritic cells, both of which can suppress T helper type 1 (Th1) responses, in the livers of two groups of mice: DO11.10 mice with transgenic CD4+ T cell receptors for OVA and BALB/c mice that received OVA-specific CD4+ T cells through adoptive transfer. This study aimed to investigate whether oral administration of OVA at high doses inhibits the development of hepatitis in the presence of OVA-specific CD4+ T cells. Oral administration of OVA at high doses inhibited the development of OVA-specific and concanavalin A (Con A)-induced hepatitis in DO11.10 mice, and these effects were associated with the downregulation of Th1 responses. Furthermore, the adoptive transfer of CD4+ T cells from the liver of OVA-fed DO11.10 mice inhibited the development of Con A-induced hepatitis in recipient BALB/c mice through the downregulation of Th1 responses. Finally, oral administration of OVA at high doses inhibited the development of Con A-induced hepatitis in BALB/c mice bearing naïve OVA-specific CD4+ T cells. These results suggest that the oral administration of antigens at high doses suppresses Th1-mediated hepatitis in an antigen-non-specific manner in the presence of antigen-specific CD4+ T cells.

Innate Immune Response Assessment in Cyprinus carpio L. upon Experimental Administration with Artemia salina Bio-Encapsulated Aeromonas hydrophila Bacterin.

The present study aimed to analyze the enhancement of innate immune responses in juvenile-stage common carp (Cyprinus carpio L.), upon the administration of heat-killed Aeromonas hydrophila at a dosage of 1 × 107 CFU ml-1 through bio-encapsulation in the aquatic crustacean, Artemia salina. This work emphasizes the modulation of innate immune response when administered with the bio-encapsulated heat-killed antigen that acts as an inactivated vaccine against Motile Aeromonas Septicemia disease. Bio-encapsulated oral administration of antigens promotes innate immunity in juvenile-stage fishes. The optimization of effective bio-encapsulation of bacterin in Artemia salina nauplii was carried out and the best optimal conditions were chosen for immunization. The functional immune parameters such as myeloperoxidase, lysozyme, alkaline phosphatase, antiprotease and respiratory burst activity in serum, blood and intestinal tissue samples were analyzed along with blood differential leukocyte count and tissue histopathology studies. Both humoral and cellular immune responses analyzed were substantially induced or enhanced in the treatment groups in comparison with the control group. The results showed a significant variation in the bio-encapsulation group than the control group and also were comparable to the protection conferred with immersion route immunization under similar conditions. Thus, most of the innate non-specific immune responses are inducible, despite being constitutive of the fish immune system, to exhibit a basal level of protection and a road to better vaccination strategy in Cyprinus carpio L. aquaculture worldwide.

Induction of antigenic immune tolerance to delay type 1 diabetes - challenges for clinical translation.

Dissect the field of antigen-specific immunotherapy (ASIT) in type 1 diabetes (T1D), highlighting the major barriers currently blocking clinical translation. ASIT remains a promising approach in T1D to re-establish the proper balance in the immune system to avoid the autoimmune-mediated attack or destruction of beta-cells in the pancreas. Despite some encouraging preclinical results, ASIT has not yet successfully translated into clinical utility, predominantly due to the lack of validated and clinically useful biomarkers. To restore immune tolerance towards self-antigens, ASIT aims to establish a favourable balance between T effector cells and T regulatory cells. Whilst most ASITs, including systemic or oral administration of relevant antigens, have appeared safe in T1D, meaningful and durable preservation of functional beta-cell mass has not been proven clinically. Development, including clinical translation, remains negatively impacted by lack of predictive biomarkers with confirmed correlation between assay readout and clinical outcomes. To be able to address the high unmet medical need in T1D, we propose continued reinforced research to identify such biomarkers, as well efforts to ensure alignment in terms of trial design and conduct.

Oral tolerance: an updated review

Oral tolerance (OT) has classically been defined as the specific suppression of cellular and/or humoral immune responses to an antigen by prior administration of the antigen through the oral route. Multiple mechanisms have been proposed to explain the induction of OT including T cell clonal depletion and anergy when high doses of antigens are fed, and regulatory T (Treg) cell generation following oral administration of low and repeated doses of antigens. Oral antigen administration suppresses the immune response in several animal models of autoimmune disease, including experimental autoimmune encephalomyelitis, uveitis, thyroiditis, myasthenia, arthritis and diabetes, but also non-autoimmune inflammatory conditions such as asthma, atherosclerosis, graft rejection, allergy and stroke. However, human trials have given mixed results and a great deal remains to be learned about the mechanisms of OT before it can be successfully applied to people. One of the possible mechanisms relates to the gut microbiota and in this review, we will explore the cellular components involved in the induction of OT and the role of the gut microbiota in contributing to OT development.

Oral administration of a peptide antigen with the cholera toxin adjuvant induces Th17 rather than Th2 cells

Abstract Cholera toxin (CT) is widely used an as adjuvant to elicit mucosal immune responses to co-administered antigens. The observation that antigens given orally with CT induce IL-4-producing T cells and antigen-specific IgE has led to the concept that CT is a Th2 adjuvant. We revisited this issue by using a peptide:MHCII tetramer-based approach to follow the fate of polyclonal CD4+ T cells specific for an MHCII-bound peptide from Toxoplasma gondii CD4Ag28m in mice fed with this peptide and CT. We found that this regimen induced the clonal expansion of CD4Ag28m peptide-specific CD4+ T cells in the secondary lymphoid organs. Surprisingly, the expanded tetramer-binding population consisted of 20 percent RORgt+ Th17 cells but only 3 percent Th2 cells. Th17 cell generation induced by oral peptide plus CT immunization was lost in mice lacking IL-6 or the microbe sensor MyD88. The latter result raised the possibility that the adjuvanticity of CT depended on gut microbes. Treatment of B6 mice with antibiotics to eradicate commensal bacteria, however, only slightly reduced Th17 cell formation in response to oral administration of the peptide plus CT, raising the possibility that viral or fungal microbes are required. Collectively, our data demonstrate that CT induces a Th17 immune response via a pathway that depends on MyD88.

Oral tolerance as antigen-specific immunotherapy.

SummaryOral tolerance is a physiological phenomenon described more than a century ago as a suppressive immune response to antigens that gain access to the body by the oral route. It is a robust and long-lasting event with local and systemic effects in which the generation of mucosally induced regulatory T cells (iTreg) plays an essential role. The idea of using oral tolerance to inhibit autoimmune and allergic diseases by oral administration of target antigens was an important development that was successfully tested in 1980s. Since then, several studies have shown that feeding specific antigens can be used to prevent and control chronic inflammatory diseases in both animal models and clinically. Therefore, oral tolerance can be classified as an antigen-specific form of oral immunotherapy (OIT). In the light of novel findings on mechanisms, sites of induction and factors affecting oral tolerance, this review will focus on specific characteristics of oral tolerance induction and how they impact in its therapeutic application.

Oral administration of antigen mainly induces T helper lineage-negative CD200+ CTLA4+ anergic CD4+ T cells which tend to become regulatory T cells

Abstract CD4+ T cells do not normally undergo productive immune responses to orally administered foreign antigens. It has been proposed that this oral tolerance phenomenon is explained by CD4+ T cells with T cell receptors (TCRs) specific for MHCII-bound peptides from ingested antigens becoming unresponsive (anergic) or differentiating into T regulatory (Treg) cells. Not much is known, however, about the phenotype and function of cells undergoing this process within the polyclonal CD4+ T cell repertoire. We addressed this issue by using I-Ab tetramers containing a foreign peptide called 2W to track 2W:I-Ab-specific CD4+ T cells after oral gavage of C57BL/6 mice with 2W peptide. These CD4+ T cells underwent weak clonal expansion when exposed orally to 2W peptide and generated a population consisting of 10% Foxp3+ Treg cells, 10% CXCR5+ follicular helper cells (Tfh), and ~3 % TBET+ Th1 or RORgt+ Th17 cells. The dominant subpopulation, however, did not express any of the known T helper cell lineage markers. Analysis of 80 surface proteins including CD73, FR4, CD200, PD-1, P2X7, and CTLA-4 revealed that these T helper lineage-negative (Thlin−) cells were more similar to anergic cells than to effector or Treg cells. In addition, adoptive transfer of sorted 2W:I-Ab-specific Thlin− cells followed by oral gavage of the peptide showed that these Foxp3− cells can become Foxp3+ Treg cells much more efficiently than naïve T cells. Collectively, our data demonstrate that the majority of CD4+ T cells exposed to oral antigen become Foxp3− anergic cells with a tendency to become Treg cells.

Co-Administration of Injected and Oral Vaccine Candidates Elicits Improved Immune Responses over Either Route Alone.

Infectious diseases continue to be a significant cause of morbidity and mortality, and although efficacious vaccines are available for many diseases, some parenteral vaccines elicit little or no mucosal antibodies which can be a significant problem since mucosal tissue is the point of entry for 90% of pathogens. In order to provide protection for both serum and mucosal areas, we have tested a combinatorial approach of both parenteral and oral administration of antigens for diseases caused by a viral pathogen, Hepatitis B, and a fungal pathogen, Coccidioides. We demonstrate that co-administration by the parenteral and oral routes is a useful tool to increase the overall immune response. This can include achieving an immune response in tissues that are not elicited when using only one route of administration, providing a higher level of response that can lead to fewer required doses or possibly providing a better response for individuals that are considered poor or non-responders.

Inducción de tolerancia por vía oral en trasplante de órganos y tejidos. Revisión de la Literatura

Introducción. La tolerancia oral es la supresión de la respuesta inmune a antígenos administrados con anterioridad por vía oral; su inducción tiene el propósito de evitar el uso de fármacos inmunosupresores, los cuales, dado que son poco específicos a antígenos, vuelven al huésped más susceptible de contraer infecciones y desarrollar neoplasias.Objetivos. Realizar una revisión de la literatura sobre los referentes teóricos más relevantes de la inducción de a tolerancia oral en lo que respecta al trasplante de órganos y tejidos para demostrar que el uso de esta alternativa terapéutica es viable en pacientes trasplantados.Materiales y métodos. Se realizó una revisión de la literatura en PubMed, MEDLINE, LILACS y Embase mediante la siguiente estrategia de búsqueda: periodo de publicación: sin límites; idiomas: Inglés y Español; tipo de artículos: estudios caso-control, revisiones sistemáticas y de la literatura; términos de búsqueda: “T-Lymphocytes, Regulatory”, “Autoimmunity”, Immunosuppression”, “Immune system” and “Immune Tolerance”, y sus equivalentes en español.Resultados. La búsqueda inicial arrojó 719 registros, sin embargo solo 99 abordaban la inducción de la tolerancia oral. Una vez los registros duplicados y los artículos sin acceso a texto completo fueron removidos, se incluyeron 72 estudios en la revisión.Conclusiones. La administración oral de antígenos es una opción efectiva para inducir tolerancia inmunológica en pacientes trasplantados (modelos murinos), pues elimina los efectos adversos que conlleva la terapia inmunosupresora actualmente utilizada.

Engineering a Nanoscale Al‐MOF‐Armored Antigen Carried by a “Trojan Horse”‐Like Platform for Oral Vaccination to Induce Potent and Long‐Lasting Immunity

AbstractVaccination via the oral administration of an antigen faces many challenges, including gastrointestinal (GI) proteolysis and mucosal barriers. To limit GI proteolysis, a biomimetically mineralized aluminum‐based metal–organic framework (Al‐MOF) system that is resistant to ambient temperature and pH and can act synergistically as a delivery vehicle and an adjuvant is synthesized over a model antigen ovalbumin (OVA) to act as armor. To overcome mucosal barriers, a yeast‐derived capsule is used to carry the Al‐MOF‐armored OVA as a “Trojan Horse”‐like transport platform. In vitro experiments reveal that the mineralization of Al‐MOFs forms an armor on OVA that protects against highly acidic and degradative GI conditions. However, the mineralized Al‐MOFs can gradually disintegrate in a phosphate ion‐containing simulated intracellular fluid, slowly releasing their encapsulated OVA. In vivo studies reveal that the “Trojan Horse”‐like transport platform specifically targets intestinal M cells, favoring the transepithelial transport of the Al‐MOF‐armored OVA, followed by subsequent endocytosis in local macrophages, ultimately accumulating in mesenteric lymph nodes, yielding long‐lasting, high‐levels of mucosal S‐IgA and serum IgG antibodies. Such an engineered delivery platform may represent a promising strategy for the oral administration of prophylactic or therapeutic antigens for vaccination.

Oral tolerance:Recent advances on mechanisms and potential applications.

Oral tolerance is a type of immune hypo-responsiveness induced by oral administration of food or harmless gastrointestinal antigens. It is evident that the induction of oral tolerance can protect our body from enteric problems, such as food allergies and colitis caused by autoimmunity. Here we review the immunological mechanisms of oral tolerance, the role of T cell cytokines in generating tolerance and the impact of Peyer's patches and mesenteric lymph nodes, and discuss the part played by commensal microflora in the regulation and maintenance of the intestinal barrier. The potential clinical applications of oral tolerance in human disease therapy are also included in this review. Understanding the mechanisms of oral tolerance may lead to the development of alternative strategies for preventing or suppressing the symptoms of autoimmune diseases and allergies.

Oral vaccination with influenza hemagglutinin combined with human pulmonary surfactant-mimicking synthetic adjuvant SF-10 induces efficient local and systemic immunity compared with nasal and subcutaneous vaccination and provides protective immunity in mice

We reported previously that a synthetic mucosal adjuvant SF-10, which mimics human pulmonary surfactant, delivers antigen to mucosal dendritic cells in the nasal cavity and promotes induction of humoral and cellular immunity. The aim of the present study was to determine the effects of oral administration of antigen combined with SF-10 (antigen-SF-10) on systemic and local immunity. Oral administration of ovalbumin, a model antigen, combined with SF-10 enhanced ovalbumin uptake into intestinal antigen presenting MHC II+CD11c+ cells and their CD11b+CD103+ and CD11b+CD103- subtype dendritic cells, which are the major antigen presenting subsets of the intestinal tract, more efficiently compared to without SF-10. Oral vaccination with influenza hemagglutinin vaccine (HAv)-SF-10 induced HAv-specific IgA and IgG in the serum, and HAv-specific secretory IgA and IgG in bronchoalveolar lavage fluid, nasal washes, gastric extracts and fecal material; their levels were significantly higher than those induced by subcutaneous HAv or intranasal HAv and HAv-SF-10 vaccinations. Enzyme-linked immunospot assay showed high numbers of HAv-specific IgA and IgG antibody secreting cells in the gastrointestinal and respiratory mucosal lymphoid tissues after oral vaccination with HAv-SF-10, but no or very low induction following oral vaccination with HAv alone. Oral vaccination with HAv-SF-10 provided protective immunity against severe influenza A virus infection, which was significantly higher than that induced by HAv combined with cholera toxin. Oral vaccination with HAv-SF-10 was associated with unique cytokine production patterns in the spleen after HAv stimulation; including marked induction of HAv-responsive Th17 cytokines (e.g., IL-17A and IL-22), high induction of Th1 cytokines (e.g., IL-2 and IFN-γ) and moderate induction of Th2 cytokines (e.g., IL-4 and IL-5). These results indicate that oral vaccination with HAv-SF-10 induces more efficient systemic and local immunity than nasal or subcutaneous vaccination with characteristically high levels of secretory HAv-specific IgA in various mucosal organs and protective immunity.

Participation of the spleen in the IgA immune response in the gut.

The role of the spleen in the induction of an immune response to orally administered antigens is still under discussion. Although it is well known that after oral antigen administration specific germinal centres are not only formed in the Peyers patches (PP) and the mesenteric lymph nodes (mLN) but also in the spleen, there is still a lack of functional data showing a direct involvement of splenic B cells in an IgA immune response in the gut. In addition, after removal of mLN a high level of IgA+ B cells was observed in the gut. Therefore, in this study we analysed the role of the spleen in the induction of IgA+ B cells in the gut after mice were orally challenged with antigens. Here we have shown that antigen specific splenic IgM+ B cells after in vitro antigen stimulation as well as oral immunisation of donor mice were able to migrate into the gut of recipient mice, where they predominantly switch to IgA+ plasma cells. Furthermore, stimulation of recipient mice by orally administered antigens enhanced the migration of the splenic B cells into the gut as well as their switch to IgA+ plasma cells. Removal of the mLN led to a higher activation level of the splenic B cells. Altogether, our results imply that splenic IgM+ B cells migrate in the intestinal lamina propria, where they differentiate into IgA+ plasma cells and subsequently proliferate. In conclusion, we demonstrated that the spleen plays a major role in the gut immune response serving as a reservoir of immune cells that migrate to the site of antigen entrance.

C5a receptor targeting of partial non-structural protein 3 of dengue virus promotes antigen-specific IFN-γ-producing T-cell responses in a mucosal dengue vaccine model

Mucosal vaccination is an ideal strategy to induce protective immunity in both mucosal and parenteral areas. Successful induction of an antigen-specific immune response via mucosal administration essentially requires the effective delivery of antigen into a mucosal immune inductive site, which depends on antigen delivery into M cells. We previously reported that M cells specifically express C5aR, and antigen targeting to C5aR by using specific ligands, including Co1 peptide, promotes the antigen-specific immune response in both mucosal and systemic immune compartments. In this study, we found that application of the Co1 peptide to dengue virus antigen containing CD8 T cell epitopes effectively induced an antigen-specific IFN-γ-producing CD8+ T cell response after oral mucosal administration of antigen. Consequently, we suggest that Co1 peptide-mediated C5aR targeting of antigen into M cells can be used for the induction of an effective antigen-specific CD8+ T cell immune response in oral mucosal vaccine development.

Cellular Components and Mechanisms of Oral Tolerance Induction.

Oral tolerance can be defined as an inhibition of specific immune responsiveness to subsequent parenteral injections of proteins to which an individual or animal has been previously exposed via the oral route. Multiple mechanisms of tolerance are induced by oral-fed antigens, but induction of regulatory CD4 T-cells expressing the transcription factor Foxp3 and the membrane-bound TGF-β stands out as the major players in oral tolerance. Oral antigen administration suppresses several animal models of autoimmune disease, including experimental autoimmune encephalomyelitis, uveitis, thyroiditis, myasthenia, arthritis, and diabetes, but also nonautoimmune inflammatory conditions such as asthma, atherosclerosis, graft rejection, allergy, and stroke. However, human trials have produced mixed results, and a great deal remains to be learned about the mechanisms of oral tolerance before it can be successfully applied to people. In this review, we highlight the cellular components involved in oral tolerance induction. A deep knowledge of these intricate cell interactions will pave the way for a successful application of antigen tolerance to treat autoimmune and nonautoimmune inflammatory diseases.

Oral tolerance modulates the skin transcriptome in mice with induced atopic dermatitis.

Defective gut immune reactions have been implicated in the development of atopic dermatitis (AD), whereas oral tolerance (OT), that is, the immune unresponsiveness induced by oral antigen administration, protects mice against AD. To investigate this protective role of OT, the transcriptomic profiles of skin were obtained by RNA sequencing from mice that were epicutaneously sensitized, orally tolerized prior to epicutaneous sensitization, or neither (control). Oral tolerance inhibited the upregulation of keratin- and allergic inflammation-associated genes that occurred in the epicutaneously sensitized group. Compared to the controls, mice that were orally tolerized and epicutaneously sensitized showed an upregulation of genes that regulate inflammation or keratinocyte differentiation. Knocking down two of those genes, SCGB1A1 and TSC22D3, upregulated Th2 inflammatory mediators and downregulated a cornified cell envelope-related gene. Based on our findings, OT may protect skin against allergic inflammation by promoting the expression of genes that regulate Th2 inflammatory responses and skin barrier function.