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Article ; Online: Common and distinct roles for T<sub>H</sub>2 and T<sub>FH</sub> cells in shaping the spectrum of allergic diseases.

Lee, Donguk / Krishnaswamy, Jayendra Kumar / Gowthaman, Uthaman

The Journal of allergy and clinical immunology

2022 Volume 150, Issue 5, Page(s) 1050–1052

MeSH term(s)	Humans ; Hypersensitivity ; T-Lymphocytes, Helper-Inducer ; Th2 Cells
Language	English
Publishing date	2022-09-26
Publishing country	United States
Document type	Editorial ; Research Support, Non-U.S. Gov't
ZDB-ID	121011-7
ISSN	1097-6825 ; 1085-8725 ; 0091-6749
ISSN (online)	1097-6825 ; 1085-8725
ISSN	0091-6749
DOI	10.1016/j.jaci.2022.09.017
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Article: The curious case of a cryptic Cryptosporidium and a missing dendritic cell subset

Lee, Donguk / Huseby, Eric S. / Gowthaman, Uthaman

Trends in parasitology. 2022 Feb., v. 38, no. 2

2022

Abstract: Animal models for studying immune responses to Cryptosporidium, a parasite that causes gastrointestinal disease, have been a challenge due to the parasite's poor infectivity in mice. Russler-Germain et al. discovered a 'commensal' strain of ... ...

Abstract	Animal models for studying immune responses to Cryptosporidium, a parasite that causes gastrointestinal disease, have been a challenge due to the parasite's poor infectivity in mice. Russler-Germain et al. discovered a 'commensal' strain of Cryptosporidium, capable of stable infection and vertical transmission, that elicits a T helper type 1 (Th1) response to promote intestinal homeostasis.
Keywords	CD4-positive T-lymphocytes ; Cryptosporidium ; dendritic cells ; gastrointestinal diseases ; homeostasis ; intestines ; parasites ; parasitology ; pathogenicity
Language	English
Dates of publication	2022-02
Size	p. 101-103.
Publishing place	Elsevier Ltd
Document type	Article
ZDB-ID	2036227-4
ISSN	1471-5007 ; 1471-4922
ISSN (online)	1471-5007
ISSN	1471-4922
DOI	10.1016/j.pt.2021.12.003
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Article ; Online: The curious case of a cryptic Cryptosporidium and a missing dendritic cell subset.

Lee, Donguk / Huseby, Eric S / Gowthaman, Uthaman

Trends in parasitology

2021 Volume 38, Issue 2, Page(s) 101–103

Abstract	Animal models for studying immune responses to Cryptosporidium, a parasite that causes gastrointestinal disease, have been a challenge due to the parasite's poor infectivity in mice. Russler-Germain et al. discovered a 'commensal' strain of Cryptosporidium, capable of stable infection and vertical transmission, that elicits a T helper type 1 (Th1) response to promote intestinal homeostasis.
MeSH term(s)	Animals ; Cryptosporidiosis/parasitology ; Cryptosporidium ; Dendritic Cells/immunology ; Homeostasis ; Intestines/parasitology ; Mice
Language	English
Publishing date	2021-12-22
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Comment
ZDB-ID	2036227-4
ISSN	1471-5007 ; 1471-4922
ISSN (online)	1471-5007
ISSN	1471-4922
DOI	10.1016/j.pt.2021.12.003
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Article ; Online: T follicular helper cells in IgE-mediated pathologies.

Gowthaman, Uthaman / Sikder, Suchandan / Lee, Donguk / Fisher, Courtney

Current opinion in immunology

2021 Volume 74, Page(s) 133–139

Abstract: T follicular helper (Tfh) cells help orchestrate optimal humoral immunity by helping B cells to produce affinity-matured, class-switched antibodies in germinal centers. Recent studies have unveiled the complexity and heterogeneity in Tfh cell populations, ...

Abstract	T follicular helper (Tfh) cells help orchestrate optimal humoral immunity by helping B cells to produce affinity-matured, class-switched antibodies in germinal centers. Recent studies have unveiled the complexity and heterogeneity in Tfh cell populations, particularly with respect to their cytokine production. These distinct Tfh cell subsets help tune the class, magnitude and quality of the immunoglobulins produced by B cells, thus shaping the course of humoral responses. The Tfh cell-B cell axis-dependent antibody production is mostly beneficial, but at times can go awry and result in the generation of pathologic antibodies that can harm the host. While IgE class of antibodies are infamous for their detrimental role in allergic diseases, emerging evidence is indicative of their pathologic roles in other dysregulated immune states. Here, we discuss the role of Tfh cell subsets in the regulation of pathologic IgE production in allergies and other immunopathologic conditions.
MeSH term(s)	B-Lymphocytes ; Cell Differentiation ; Germinal Center ; Humans ; Hypersensitivity ; Immunoglobulin E ; T Follicular Helper Cells ; T-Lymphocytes, Helper-Inducer
Chemical Substances	Immunoglobulin E (37341-29-0)
Language	English
Publishing date	2021-12-21
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1035767-1
ISSN	1879-0372 ; 0952-7915
ISSN (online)	1879-0372
ISSN	0952-7915
DOI	10.1016/j.coi.2021.12.001
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Article ; Online: Regulation of IgE by T follicular helper cells.

Gowthaman, Uthaman / Chen, Jennifer S / Eisenbarth, Stephanie C

Journal of leukocyte biology

2020 Volume 107, Issue 3, Page(s) 409–418

Abstract: Allergies to food and environmental antigens have steeply grown to epidemic proportions. IgE antibodies are key mediators of allergic disease, including life-threatening anaphylaxis. There is now compelling evidence that one of the hallmarks of ... ...

Abstract	Allergies to food and environmental antigens have steeply grown to epidemic proportions. IgE antibodies are key mediators of allergic disease, including life-threatening anaphylaxis. There is now compelling evidence that one of the hallmarks of anaphylaxis-inducing IgE molecules is their high affinity for allergen, and the cellular pathway to high-affinity IgE is typically through sequential switching of IgG B cells. Further, in contrast to the previously held paradigm that a subset of CD4
MeSH term(s)	Anaphylaxis/immunology ; Anaphylaxis/parasitology ; Animals ; Cell Differentiation ; Cell Plasticity ; Humans ; Hypersensitivity/immunology ; Hypersensitivity/parasitology ; Immunoglobulin E/metabolism ; T-Lymphocytes, Helper-Inducer/immunology
Chemical Substances	Immunoglobulin E (37341-29-0)
Language	English
Publishing date	2020-01-22
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	605722-6
ISSN	1938-3673 ; 0741-5400
ISSN (online)	1938-3673
ISSN	0741-5400
DOI	10.1002/JLB.3RI1219-425R
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Article ; Online: Molecular mimicry: good artists copy, great artists steal.

Gowthaman, Uthaman / Eswarakumar, Veraragavan P

Virulence

2013 Volume 4, Issue 6, Page(s) 433–434

MeSH term(s)	Bacteria/genetics ; Bacteria/metabolism ; Bacterial Infections/genetics ; Bacterial Infections/immunology ; Bacterial Infections/microbiology ; Bacterial Proteins/genetics ; Bacterial Proteins/metabolism ; Host-Pathogen Interactions ; Humans ; Molecular Mimicry ; Virulence Factors/genetics ; Virulence Factors/metabolism
Chemical Substances	Bacterial Proteins ; Virulence Factors
Language	English
Publishing date	2013-07-17
Publishing country	United States
Document type	Editorial
ZDB-ID	2657572-3
ISSN	2150-5608 ; 2150-5594
ISSN (online)	2150-5608
ISSN	2150-5594
DOI	10.4161/viru.25780
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Article ; Online: Flow cytometric identification of T

Chen, Jennifer S / Grassmann, Jessica D S / Gowthaman, Uthaman / Olyha, Sam J / Simoneau, Tregony / Berin, M Cecilia / Eisenbarth, Stephanie C / Williams, Adam

The Journal of allergy and clinical immunology

2020 Volume 147, Issue 2, Page(s) 470–483

Abstract: Anaphylaxis is a life-threatening allergic reaction caused by cross-linking of high-affinity IgE antibodies on the surface of mast cells and basophils. Understanding the cellular mechanisms that lead to high-affinity IgE production is required to develop ...

Abstract	Anaphylaxis is a life-threatening allergic reaction caused by cross-linking of high-affinity IgE antibodies on the surface of mast cells and basophils. Understanding the cellular mechanisms that lead to high-affinity IgE production is required to develop better therapeutics for preventing this severe reaction. A recently discovered population of T follicular helper T
MeSH term(s)	Animals ; Cell Separation/methods ; Flow Cytometry/methods ; Humans ; Mice ; T Follicular Helper Cells ; T-Lymphocyte Subsets
Keywords	covid19
Language	English
Publishing date	2020-07-21
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	121011-7
ISSN	1097-6825 ; 1085-8725 ; 0091-6749
ISSN (online)	1097-6825 ; 1085-8725
ISSN	0091-6749
DOI	10.1016/j.jaci.2020.04.063
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Article ; Online: In silico methods for predicting T-cell epitopes: Dr Jekyll or Mr Hyde?

Gowthaman, Uthaman / Agrewala, Javed N

Expert review of proteomics

2009 Volume 6, Issue 5, Page(s) 527–537

Abstract: In silico tools offer an attractive alternative strategy to the cumbersome experimental approaches to identify T-cell epitopes. These computational tools have metamorphosed over the years into complex algorithms that attempt to efficiently predict the ... ...

Abstract	In silico tools offer an attractive alternative strategy to the cumbersome experimental approaches to identify T-cell epitopes. These computational tools have metamorphosed over the years into complex algorithms that attempt to efficiently predict the binding of a plethora of peptides to HLA alleles. In recent years, the scientific community has embraced these techniques to reduce the burden of wet-laboratory experimentation. Although there are some splendid examples of the utility of these methods, there are also evidences where they fall short and remain inconsistent. Hence, are these computational tools 'Dr Jekyll' or 'Mr Hyde' to the researcher, who wishes to utilize them intrepidly? This article reviews the progress and pitfalls of the in silico tools that identify T-cell epitopes.
MeSH term(s)	Algorithms ; Epitopes/immunology ; HLA Antigens/immunology ; Humans ; Markov Chains ; Neural Networks (Computer) ; T-Lymphocytes/immunology
Chemical Substances	Epitopes ; HLA Antigens
Language	English
Publishing date	2009-10
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2299100-1
ISSN	1744-8387 ; 1478-9450
ISSN (online)	1744-8387
ISSN	1478-9450
DOI	10.1586/epr.09.71
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Article ; Online: Oral anaphylaxis to peanut in a mouse model is associated with gut permeability but not with Tlr4 or Dock8 mutations.

Gertie, Jake A / Zhang, Biyan / Liu, Elise G / Hoyt, Laura R / Yin, Xiangyun / Xu, Lan / Long, Lauren L / Soldatenko, Arielle / Gowthaman, Uthaman / Williams, Adam / Eisenbarth, Stephanie C

The Journal of allergy and clinical immunology

2021 Volume 149, Issue 1, Page(s) 262–274

Abstract: Background: The etiology of food allergy is poorly understood; mouse models are powerful systems to discover immunologic pathways driving allergic disease. C3H/HeJ mice are a widely used model for the study of peanut allergy because, unlike C57BL/6 or ... ...

Abstract	Background: The etiology of food allergy is poorly understood; mouse models are powerful systems to discover immunologic pathways driving allergic disease. C3H/HeJ mice are a widely used model for the study of peanut allergy because, unlike C57BL/6 or BALB/c mice, they are highly susceptible to oral anaphylaxis. However, the immunologic mechanism of this strain's susceptibility is not known. Objective: We aimed to determine the mechanism underlying the unique susceptibility to anaphylaxis in C3H/HeJ mice. We tested the role of deleterious Toll-like receptor 4 (Tlr4) or dedicator of cytokinesis 8 (Dock8) mutations in this strain because both genes have been associated with food allergy. Methods: We generated C3H/HeJ mice with corrected Dock8 or Tlr4 alleles and sensitized and challenged them with peanut. We then characterized the antibody response to sensitization, anaphylaxis response to both oral and systemic peanut challenge, gut microbiome, and biomarkers of gut permeability. Results: In contrast to C3H/HeJ mice, C57BL/6 mice were resistant to anaphylaxis after oral peanut challenge; however, both strains undergo anaphylaxis with intraperitoneal challenge. Restoring Tlr4 or Dock8 function in C3H/HeJ mice did not protect from anaphylaxis. Instead, we discovered enhanced gut permeability resulting in ingested allergens in the bloodstream in C3H/HeJ mice compared to C57BL/6 mice, which correlated with an increased number of goblet cells in the small intestine. Conclusions: Our work highlights the potential importance of gut permeability in driving anaphylaxis to ingested food allergens; it also indicates that genetic loci outside of Tlr4 and Dock8 are responsible for the oral anaphylactic susceptibility of C3H/HeJ mice.
MeSH term(s)	Administration, Oral ; Animals ; Arachis/immunology ; Disease Models, Animal ; Female ; Gastrointestinal Microbiome ; Genetic Predisposition to Disease ; Guanine Nucleotide Exchange Factors/genetics ; Intestinal Mucosa/metabolism ; Male ; Mice, Inbred C3H ; Mice, Inbred C57BL ; Mutation ; Passive Cutaneous Anaphylaxis/genetics ; Peanut Hypersensitivity/genetics ; Peanut Hypersensitivity/metabolism ; Peanut Hypersensitivity/microbiology ; Permeability ; Species Specificity ; Toll-Like Receptor 4/genetics ; Mice
Chemical Substances	Dock8 protein, mouse ; Guanine Nucleotide Exchange Factors ; Tlr4 protein, mouse ; Toll-Like Receptor 4
Language	English
Publishing date	2021-05-27
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	121011-7
ISSN	1097-6825 ; 1085-8725 ; 0091-6749
ISSN (online)	1097-6825 ; 1085-8725
ISSN	0091-6749
DOI	10.1016/j.jaci.2021.05.015
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Article: In silico tools for predicting peptides binding to HLA-class II molecules: more confusion than conclusion.

Gowthaman, Uthaman / Agrewala, Javed N

Journal of proteome research

2008 Volume 7, Issue 1, Page(s) 154–163

Abstract: Identification of promiscuous peptides, which bind to human leukocyte antigen, is indispensable for global vaccination. However, the development of such vaccines is impaired due to the exhaustive polymorphism in human leukocyte antigens. The use of in ... ...

Abstract	Identification of promiscuous peptides, which bind to human leukocyte antigen, is indispensable for global vaccination. However, the development of such vaccines is impaired due to the exhaustive polymorphism in human leukocyte antigens. The use of in silico tools for mining such peptides circumvents the expensive and laborious experimental screening methods. Nevertheless, the intrepid use of such tools warrants a rational assessment with respect to experimental findings. Here, we have adopted a 'bottom up' approach, where we have used experimental data to assess the reliability of existing in silico methods. We have used a data set of 179 peptides from diverse antigens and have validated six commonly used in silico methods; ProPred, MHC2PRED, RANKPEP, SVMHC, MHCPred, and MHC-BPS. We observe that the prediction efficiency of the programs is not balanced for all the HLA-DR alleles and there is extremely high level of discrepancy in the prediction efficiency apropos of the nature of the antigen. It has not escaped our notice that the in silico methods studied here are not very proficient in identifying promiscuous peptides. This puts a much constraint on the intrepid use of such programs for human leukocyte antigen class II binding peptides. We conclude from this study that the in silico methods cannot be wholly relied for selecting crucial peptides for development of vaccines.
MeSH term(s)	Antigens/metabolism ; Computational Biology/methods ; Histocompatibility Antigens Class II/metabolism ; Humans ; Peptides/metabolism ; Protein Binding ; Software/standards ; Vaccines
Chemical Substances	Antigens ; Histocompatibility Antigens Class II ; Peptides ; Vaccines
Language	English
Publishing date	2008-01
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2078618-9
ISSN	1535-3893
ISSN	1535-3893
DOI	10.1021/pr070527b
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