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Article ; Online: Profiling of Tregs across tissues reveals plasticity in ST2 expression and hierarchies in tissue-specific phenotypes.

Spath, Sabine / Roan, Florence / Presnell, Scott R / Höllbacher, Barbara / Ziegler, Steven F

iScience

2022 Volume 25, Issue 9, Page(s) 104998

Abstract: ... ...

Abstract	Foxp3
Language	English
Publishing date	2022-08-24
Publishing country	United States
Document type	Journal Article
ISSN	2589-0042
ISSN (online)	2589-0042
DOI	10.1016/j.isci.2022.104998
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Article ; Online: Human Group 1 Innate Lymphocytes Are Negative for Surface CD3ε but Express CD5.

Roan, Florence / Ziegler, Steven F

Immunity

2017 Volume 46, Issue 5, Page(s) 758–759

Language	English
Publishing date	2017-05-16
Publishing country	United States
Document type	Letter
ZDB-ID	1217235-2
ISSN	1097-4180 ; 1074-7613
ISSN (online)	1097-4180
ISSN	1074-7613
DOI	10.1016/j.immuni.2017.04.024
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Article ; Online: Epithelial cell-derived cytokines: more than just signaling the alarm.

Roan, Florence / Obata-Ninomiya, Kazushige / Ziegler, Steven F

The Journal of clinical investigation

2019 Volume 129, Issue 4, Page(s) 1441–1451

Abstract: The epithelial cell-derived cytokines thymic stromal lymphopoietin (TSLP), IL-33, and IL-25 are central regulators of type 2 immunity, which drives a broad array of allergic responses. Often characterized as "alarmins" that are released by the barrier ... ...

Abstract	The epithelial cell-derived cytokines thymic stromal lymphopoietin (TSLP), IL-33, and IL-25 are central regulators of type 2 immunity, which drives a broad array of allergic responses. Often characterized as "alarmins" that are released by the barrier epithelium in response to external insults, these epithelial cell-derived cytokines were initially thought to act only early in allergic inflammation. Indeed, TSLP can condition dendritic cells to initiate type 2 responses, and IL-33 may influence susceptibility to asthma through its role in establishing the immune environment in the perinatal lungs. However, TSLP, IL-33, and IL-25 all regulate a broad spectrum of innate immune cell populations and are particularly potent in eliciting and activating type 2 innate lymphoid cells (ILC2s) that may act throughout allergic inflammation. Recent data suggest that a TSLP/ILC axis may mediate steroid resistance in asthma. Recent identification of memory Th2 cell subsets that are characterized by high receptor expression for TSLP, IL-33, and IL-25 further supports a role for these cytokines in allergic exacerbations. There is therefore growing interest in developing biologics that target TSLP, IL-33, and IL-25. This Review provides an overview of TSLP, IL-33, and IL-25 and the development of blocking antibodies that target these epithelial cell-derived cytokines.
MeSH term(s)	Animals ; Cytokines/immunology ; Epithelial Cells/immunology ; Epithelial Cells/pathology ; Humans ; Hypersensitivity/immunology ; Hypersensitivity/pathology ; Immunity, Innate ; Lymphocytes/immunology ; Lymphocytes/pathology
Chemical Substances	Cytokines
Language	English
Publishing date	2019-04-01
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	3067-3
ISSN	1558-8238 ; 0021-9738
ISSN (online)	1558-8238
ISSN	0021-9738
DOI	10.1172/JCI124606
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Article ; Online: The atopic march: current insights into skin barrier dysfunction and epithelial cell-derived cytokines.

Han, Hongwei / Roan, Florence / Ziegler, Steven F

Immunological reviews

2017 Volume 278, Issue 1, Page(s) 116–130

Abstract: Atopic dermatitis often precedes the development of other atopic diseases. The atopic march describes this temporal relationship in the natural history of atopic diseases. Although the pathophysiological mechanisms that underlie this relationship are ... ...

Abstract	Atopic dermatitis often precedes the development of other atopic diseases. The atopic march describes this temporal relationship in the natural history of atopic diseases. Although the pathophysiological mechanisms that underlie this relationship are poorly understood, epidemiological and genetic data have suggested that the skin might be an important route of sensitization to allergens. Animal models have begun to elucidate how skin barrier defects can lead to systemic allergen sensitization. Emerging data now suggest that epithelial cell-derived cytokines such as thymic stromal lymphopoietin (TSLP), IL-33, and IL-25 may drive the progression from atopic dermatitis to asthma and food allergy. This review focuses on current concepts of the role of skin barrier defects and epithelial cell-derived cytokines in the initiation and maintenance of allergic inflammation and the atopic march.
MeSH term(s)	Allergens/immunology ; Animals ; Cytokines/metabolism ; Dermatitis, Atopic/etiology ; Dermatitis, Atopic/metabolism ; Dermatitis, Atopic/pathology ; Dermatitis, Atopic/therapy ; Environment ; Epithelial Cells/metabolism ; Genetic Predisposition to Disease ; Humans ; Immune Tolerance/immunology ; Immunization ; Immunotherapy ; Skin/immunology ; Skin/metabolism ; Skin/pathology
Chemical Substances	Allergens ; Cytokines
Language	English
Publishing date	2017
Publishing country	England
Document type	Journal Article ; Review ; Research Support, N.I.H., Extramural
ZDB-ID	391796-4
ISSN	1600-065X ; 0105-2896
ISSN (online)	1600-065X
ISSN	0105-2896
DOI	10.1111/imr.12546
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Article ; Online: KAP1 Regulates Regulatory T Cell Function and Proliferation in Both Foxp3-Dependent and -Independent Manners.

Tanaka, Shigeru / Pfleger, Christian / Lai, Jen-Feng / Roan, Florence / Sun, Shao-Cong / Ziegler, Steven F

Cell reports

2018 Volume 23, Issue 3, Page(s) 796–807

Abstract: Regulatory T cells (Tregs) are indispensable for the establishment of tolerance of self-antigens in animals. The transcriptional regulator Foxp3 is critical for Treg development and function, controlling the expression of genes important for Tregs ... ...

Abstract	Regulatory T cells (Tregs) are indispensable for the establishment of tolerance of self-antigens in animals. The transcriptional regulator Foxp3 is critical for Treg development and function, controlling the expression of genes important for Tregs through interactions with binding partners. We previously reported KAP1 as a binding partner of FOXP3 in human Tregs, but the mechanisms by which KAP1 affects Treg function were unclear. In this study, we analyzed mice with Treg-specific deletion of KAP1 and found that they develop spontaneous autoimmune disease. KAP1-deficient Tregs failed to induce Foxp3-regulated Treg signature genes. In addition, KAP1-deficient Tregs were less proliferative due to the decreased expression of Slc1a5, whose expression was KAP1 dependent but Foxp3 independent. This reduced expression of Slc1a5 resulted in reduced mTORC1 activation. Thus, our data suggest that KAP1 regulates Treg function in a Foxp3-dependent manner and also controls Treg proliferation in a Foxp3-independent manner.
MeSH term(s)	Amino Acid Transport System ASC/metabolism ; Animals ; Autoimmune Diseases/etiology ; Autoimmune Diseases/metabolism ; Autoimmune Diseases/veterinary ; Binding Sites ; Cell Proliferation ; Core Binding Factor Alpha 2 Subunit/chemistry ; Core Binding Factor Alpha 2 Subunit/metabolism ; Down-Regulation ; Forkhead Transcription Factors/genetics ; Forkhead Transcription Factors/metabolism ; Homeodomain Proteins/genetics ; Lung/immunology ; Lung/metabolism ; Mechanistic Target of Rapamycin Complex 1/metabolism ; Mice ; Mice, Knockout ; Mice, Transgenic ; Minor Histocompatibility Antigens/metabolism ; Protein Binding ; T-Lymphocytes, Regulatory/cytology ; T-Lymphocytes, Regulatory/immunology ; T-Lymphocytes, Regulatory/metabolism ; Tripartite Motif-Containing Protein 28/deficiency ; Tripartite Motif-Containing Protein 28/genetics ; Tripartite Motif-Containing Protein 28/metabolism
Chemical Substances	Amino Acid Transport System ASC ; Core Binding Factor Alpha 2 Subunit ; Forkhead Transcription Factors ; Foxp3 protein, mouse ; Homeodomain Proteins ; Minor Histocompatibility Antigens ; Runx1 protein, mouse ; Slc1a5 protein, mouse ; RAG-1 protein (128559-51-3) ; Trim28 protein, mouse (EC 2.3.2.27) ; Tripartite Motif-Containing Protein 28 (EC 2.3.2.27) ; Mechanistic Target of Rapamycin Complex 1 (EC 2.7.11.1)
Language	English
Publishing date	2018-12-15
Publishing country	United States
Document type	Journal Article
ZDB-ID	2649101-1
ISSN	2211-1247 ; 2211-1247
ISSN (online)	2211-1247
ISSN	2211-1247
DOI	10.1016/j.celrep.2018.03.099
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Article ; Online: Correction: CD4+ Group 1 Innate Lymphoid Cells (ILC) Form a Functionally Distinct ILC Subset That Is Increased in Systemic Sclerosis.

Roan, Florence / Stoklasek, Thomas A / Whalen, Elizabeth / Molitor, Jerry A / Bluestone, Jeffrey A / Buckner, Jane H / Ziegler, Steven F

Journal of immunology (Baltimore, Md. : 1950)

2016 Volume 196, Issue 9, Page(s) 3966

Language	English
Publishing date	2016-05-13
Publishing country	United States
Document type	Journal Article ; Published Erratum
ZDB-ID	3056-9
ISSN	1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
ISSN (online)	1550-6606
ISSN	0022-1767 ; 1048-3233 ; 1047-7381
DOI	10.4049/jimmunol.1600364
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Article ; Online: CD4+ Group 1 Innate Lymphoid Cells (ILC) Form a Functionally Distinct ILC Subset That Is Increased in Systemic Sclerosis.

Roan, Florence / Stoklasek, Thomas A / Whalen, Elizabeth / Molitor, Jerry A / Bluestone, Jeffrey A / Buckner, Jane H / Ziegler, Steven F

Journal of immunology (Baltimore, Md. : 1950)

2016 Volume 196, Issue 5, Page(s) 2051–2062

Abstract: Innate lymphoid cells (ILC) are a heterogeneous group of cellular subsets that produce large amounts of T cell-associated cytokines in response to innate stimulation in the absence of Ag. In this study, we define distinct patterns of surface marker and ... ...

Abstract	Innate lymphoid cells (ILC) are a heterogeneous group of cellular subsets that produce large amounts of T cell-associated cytokines in response to innate stimulation in the absence of Ag. In this study, we define distinct patterns of surface marker and cytokine expression among the ILC subsets that may further delineate their migration and function. Most notably, we found that the subset previously defined as group 1 ILC (ILC1) contains CD4(+) CD8(-), CD4(-) CD8(+), and CD4(-) CD8(-) populations. Although all ILC1 subsets shared characteristics with Th1 cells, CD4(+) ILC1 also demonstrated significant phenotypic and functional heterogeneity. We also show that the frequencies of CD4(+) ILC1 and NKp44(+) group 3 ILC, but not CD4(-) ILC1 or group 2 ILC, are increased in the peripheral blood of individuals with systemic sclerosis (SSc), a disease characterized by fibrotic and vascular pathology, as well as immune dysregulation. Furthermore, we demonstrate that CD4(+) and CD4(-) ILC1 are functionally divergent based on their IL-6Rα expression and that the frequency of IL-6Rα expression on ILC is altered in SSc. The distinct phenotypic and functional features of CD4(+) and CD4(-) ILC1 suggest that they may have differing roles in the pathogenesis of immune-mediated diseases, such as SSc.
MeSH term(s)	CD4-Positive T-Lymphocytes/immunology ; Cell Separation ; Flow Cytometry ; Humans ; Oligonucleotide Array Sequence Analysis ; Scleroderma, Systemic/immunology ; T-Lymphocyte Subsets/immunology
Language	English
Publishing date	2016-01-29
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	3056-9
ISSN	1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
ISSN (online)	1550-6606
ISSN	0022-1767 ; 1048-3233 ; 1047-7381
DOI	10.4049/jimmunol.1501491
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Article ; Online: The biology of thymic stromal lymphopoietin (TSLP).

Ziegler, Steven F / Roan, Florence / Bell, Bryan D / Stoklasek, Thomas A / Kitajima, Masayuki / Han, Hongwei

Advances in pharmacology (San Diego, Calif.)

2013 Volume 66, Page(s) 129–155

Abstract: Originally shown to promote the growth and activation of B cells, thymic stromal lymphopoietin (TSLP) is now known to have wide-ranging impacts on both hematopoietic and nonhematopoietic cell lineages, including dendritic cells, basophils, eosinophils, ... ...

Abstract	Originally shown to promote the growth and activation of B cells, thymic stromal lymphopoietin (TSLP) is now known to have wide-ranging impacts on both hematopoietic and nonhematopoietic cell lineages, including dendritic cells, basophils, eosinophils, mast cells, CD4⁺, CD8⁺ and natural killer T cells, B cells and epithelial cells. While TSLP's role in the promotion of TH2 responses has been extensively studied in the context of lung- and skin-specific allergic disorders, it is becoming increasingly clear that TSLP may impact multiple disease states within multiple organ systems, including the blockade of TH1/TH17 responses and the promotion of cancer and autoimmunity. This chapter will highlight recent advances in the understanding of TSLP signal transduction, as well as the role of TSLP in allergy, autoimmunity and cancer. Importantly, these insights into TSLP's multifaceted roles could potentially allow for novel therapeutic manipulations of these disorders.
MeSH term(s)	Animals ; Cytokines/metabolism ; Humans ; Immune System/immunology ; Immune System/metabolism ; Immune System Diseases/immunology ; Immune System Diseases/metabolism ; Neoplasm Proteins/metabolism ; Neoplasms/immunology ; Neoplasms/metabolism ; Receptors, Cytokine/metabolism ; Signal Transduction
Chemical Substances	CRLF2 protein, human ; Cytokines ; Neoplasm Proteins ; Receptors, Cytokine ; thymic stromal lymphopoietin (GT0IL38SP4)
Language	English
Publishing date	2013-02-22
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ISSN	1557-8925
ISSN (online)	1557-8925
DOI	10.1016/B978-0-12-404717-4.00004-4
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Article ; Online: The multiple facets of thymic stromal lymphopoietin (TSLP) during allergic inflammation and beyond.

Roan, Florence / Bell, Bryan D / Stoklasek, Thomas A / Kitajima, Masayuki / Han, Hongwei / Ziegler, Steven F

Journal of leukocyte biology

2012 Volume 91, Issue 6, Page(s) 877–886

Abstract: Originally shown to promote the growth and activation of B cells, TSLP is now known to have wide-ranging impacts on hematopoietic and nonhematopoietic cell lineages, including DCs, basophils, eosinophils, mast cells, CD4(+), CD8(+), and NK T cells, B ... ...

Abstract	Originally shown to promote the growth and activation of B cells, TSLP is now known to have wide-ranging impacts on hematopoietic and nonhematopoietic cell lineages, including DCs, basophils, eosinophils, mast cells, CD4(+), CD8(+), and NK T cells, B cells, and epithelial cells. Whereas the role of TSLP in the promotion of TH2 responses has been studied extensively in the context of lung- and skin-specific allergic disorders, it is becoming increasingly clear that TSLP may impact multiple disease states within multiple organ systems, including the blockade of TH1/TH17 responses and the promotion of cancer and autoimmunity. This review will highlight recent advances in the understanding of TSLP signal transduction, as well as the role of TSLP in allergy, autoimmunity, and cancer. Importantly, these insights into the multifaceted roles of TSLP could potentially allow for novel, therapeutic manipulations of these disorders.
MeSH term(s)	Animals ; Autoimmune Diseases/immunology ; Autoimmune Diseases/pathology ; Cytokines/immunology ; Dendritic Cells/immunology ; Dendritic Cells/pathology ; Humans ; Hypersensitivity/immunology ; Hypersensitivity/pathology ; Inflammation/immunology ; Inflammation/pathology ; Leukocytes/immunology ; Leukocytes/pathology ; Neoplasms/immunology ; Neoplasms/pathology ; Signal Transduction/immunology
Chemical Substances	Cytokines ; thymic stromal lymphopoietin (GT0IL38SP4)
Language	English
Publishing date	2012-03-21
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	10.1189/jlb.1211622
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Article: Activation of cellular and heterologous promoters by the human herpesvirus 8 replication and transcription activator.

Roan, Florence / Inoue, Naoki / Offermann, Margaret K

Virology

2002 Volume 301, Issue 2, Page(s) 293–304

Abstract: The key regulator of the switch from latent to lytic replication of the human herpesvirus 8 (HHV-8; KSHV) is the replication and transcription activator (Rta). The ability of Rta to regulate cellular gene expression was examined by transient transfection ...

Abstract	The key regulator of the switch from latent to lytic replication of the human herpesvirus 8 (HHV-8; KSHV) is the replication and transcription activator (Rta). The ability of Rta to regulate cellular gene expression was examined by transient transfection into cells that were not infected with HHV-8. Rta induced some, but not all, NF-kappa B-responsive reporters through mechanisms that did not involve activation of classic forms of NF-kappa B. Furthermore, transfection of the NF-kappa B subunit Rel A inhibited the ability of Rta to transactivate some but not all reporters. For example, Rel A inhibited the ability of Rta to transactivate the IL-6 promoter, but only when sequences upstream of the NF-kappa B site were present. The ability of Rel A to inhibit Rta-mediated transactivation was not dependent on a functional NF-kappa B site within the promoter, suggesting an indirect mechanism for inhibition. These studies suggest that Rta expression during lytic reactivation of HHV-8 would lead to expression of some cellular genes, including IL-6, whereas activation of NF-kappa B could inhibit some responses to Rta.
MeSH term(s)	Binding Sites ; Cell Line, Transformed ; Chloramphenicol O-Acetyltransferase/genetics ; Genes, Reporter ; HIV/genetics ; HIV Enhancer ; HeLa Cells ; Herpesvirus 8, Human/metabolism ; Herpesvirus 8, Human/physiology ; Humans ; Immediate-Early Proteins/genetics ; Immediate-Early Proteins/metabolism ; Interleukin-6/genetics ; Interleukin-6/metabolism ; NF-kappa B/metabolism ; Promoter Regions, Genetic ; Response Elements ; Trans-Activators/genetics ; Trans-Activators/metabolism ; Transcription Factor RelA ; Transcriptional Activation ; Viral Proteins/genetics ; Viral Proteins/metabolism ; Virus Replication/physiology
Chemical Substances	Immediate-Early Proteins ; Interleukin-6 ; NF-kappa B ; Rta protein, Human herpesvirus 8 ; Trans-Activators ; Transcription Factor RelA ; Viral Proteins ; Chloramphenicol O-Acetyltransferase (EC 2.3.1.28)
Language	English
Publishing date	2002-09-30
Publishing country	United States
Document type	Journal Article ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	200425-2
ISSN	1096-0341 ; 0042-6822
ISSN (online)	1096-0341
ISSN	0042-6822
DOI	10.1006/viro.2002.1582
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