title: Cutaneous exposure to clinically-relevant pigeon pea (Cajanus cajan) proteins promote TH2-dependent sensitization and IgE-mediated anaphylaxis in Balb/c mice.
abstract: Epicutaneous (EC) sensitization to food allergens may occur when the skin has been lightly damaged. The study here tested whether cutaneous exposure to pigeon pea protein(s) may cause allergic sensitization. BALB/c mice were either orally gavaged or epicutaneously sensitized by repeated application of pigeon pea crude protein extract (CPE) on undamaged areas of skin without any adjuvant; afterwards, both groups were orally challenged with the pigeon pea CPE. Anaphylactic symptoms along with measures of body temperature, MCPT-1, TSLP, pigeon pea-specific IgE and IgG1, myeloperoxidase (MPO) activity, TH2 cytokines, TH2 transcription factors (TFs) and filaggrin expression were determined. Mast cell staining, eosinophil levels and histopathological analysis of the skin and intestines were also performed. In the epicutaneously-sensitized mice, elevated levels of specific IgE and IgG1, as well as of MCPT-1, TSLP, TH2 cytokines and TFs, higher anaphylactic scores and histological changes in the skin and intestine were indicative of sensitization ability via both routes in the pigeon pea CPE-treated hosts. Elevated levels of mast cells were observed in both the skin and intestine; increased levels of eosinophils and MPO activity were noted only in the skin. Decreased levels of filaggrin in skin may have played a key role in the skin barrier dysfunction, increasing the chances of sensitization. Therefore, the experimental data support the hypothesis that in addition to oral exposure, skin exposure to food allergens can promote TH2-dependent sensitization, IgE-mediated anaphylaxis and intestinal changes after oral challenge. Based on this, an avoidance of cutaneous exposures to allergens might prevent development of food anaphylaxis.
authors.affiliation: a Food Toxicology Laboratory, Food, Drug and Chemical Toxicology Group, CSIR-Indian Institute of Toxicology Research (CSIR-IITR) , Lucknow , India.|g Department of Biosciences , Integral University , Lucknow , India.
authors.forename: Rinkesh
authors.initials: R
authors.lastname: Kumar Gupta
authors.affiliation: b Division of Surgical Oncology, Department of Surgery , University of Illinois at Chicago , USA.
authors.forename: Sandeep
authors.initials: S
authors.lastname: Kumar
authors.affiliation: a Food Toxicology Laboratory, Food, Drug and Chemical Toxicology Group, CSIR-Indian Institute of Toxicology Research (CSIR-IITR) , Lucknow , India.
authors.forename: Kriti
authors.initials: K
authors.lastname: Gupta
authors.affiliation: a Food Toxicology Laboratory, Food, Drug and Chemical Toxicology Group, CSIR-Indian Institute of Toxicology Research (CSIR-IITR) , Lucknow , India.|c Academy of Scientific and Innovative Research (AcSIR), CSIR-Indian Institute of Toxicology Research (CSIR-IITR) , Lucknow , India.
authors.forename: Akanksha
authors.initials: A
authors.lastname: Sharma
authors.affiliation: d Pharmacology and Chemical Biology Department , Hillman Cancer Center, University of Pittsburgh , Pittsburgh , PA , USA.
authors.forename: Ruchi
authors.initials: R
authors.lastname: Roy
authors.affiliation: e Section of Department of Medicine, Pulmonary Diseases, Tulane Eosinophilic Disorder Center, Tulane University , New Orleans , LA , USA.
authors.forename: Alok
authors.initials: A
authors.lastname: Kumar Verma
authors.affiliation: f Biochemical Sciences Division , CSIR-National Chemical Laboratory , Pune , Maharashtra , India.
authors.forename: Bhushan P
authors.initials: BP
authors.lastname: Chaudhari
authors.affiliation: a Food Toxicology Laboratory, Food, Drug and Chemical Toxicology Group, CSIR-Indian Institute of Toxicology Research (CSIR-IITR) , Lucknow , India.|c Academy of Scientific and Innovative Research (AcSIR), CSIR-Indian Institute of Toxicology Research (CSIR-IITR) , Lucknow , India.
authors.forename: Mukul
authors.initials: M
authors.lastname: Das
authors.affiliation: g Department of Biosciences , Integral University , Lucknow , India.
authors.forename: Irfan
authors.initials: I
authors.lastname: Ahmad Ansari
authors.affiliation: a Food Toxicology Laboratory, Food, Drug and Chemical Toxicology Group, CSIR-Indian Institute of Toxicology Research (CSIR-IITR) , Lucknow , India.|c Academy of Scientific and Innovative Research (AcSIR), CSIR-Indian Institute of Toxicology Research (CSIR-IITR) , Lucknow , India.
authors.forename: Premendra D
authors.initials: PD
authors.lastname: Dwivedi
mesh_terms: D000485:Allergens / Q000276:immunology; D000707:Anaphylaxis / Q000276:immunology*; D000818:Animals; D052179:Antigens, Plant / Q000276:immunology; D036561:Cajanus / Q000276:immunology; D002478:Cells, Cultured; D053818:Chymases / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004804:Eosinophils / Q000276:immunology*; D000091344:Filaggrin Proteins; D005512:Food Hypersensitivity / Q000276:immunology*; D006801:Humans; D007114:Immunization; D007073:Immunoglobulin E / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D010936:Plant Extracts / Q000276:immunology; D012867:Skin / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
chemical_list: D000485:Allergens; D052179:Antigens, Plant; D016207:Cytokines; C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D010936:Plant Extracts; D007073:Immunoglobulin E; D053818:Chymases; C509230:Mcpt1 protein, mouse
keywords: Anaphylaxis; allergen; mast cell; pigeon pea