Anna L. Furmanski, Ryan F. L

Slides:

Advertisements

Similar presentations

William H. D. Hallett, Weiqing Jing, William R. Drobyski, Bryon D

Advertisements

Histologic Study of the Regeneration Process of Human Hair Follicles Grafted onto SCID Mice after Bulb Amputation Tsuyoshi Hashimoto, Takashi Kazama,

Disrupted Ectodermal Organ Morphogenesis in Mice with a Conditional Histone Deacetylase 1, 2 Deletion in the Epidermis Michael W. Hughes, Ting-Xin Jiang,

Exacerbated colitis associated with elevated levels of activated CD4+ T cells in TCRα chain transgenic mice Immo Prinz, Uwe Klemm, Stefan H.E. Kaufmann,

Identification of CD3+CD4−CD8− T Cells as Potential Regulatory Cells in an Experimental Murine Model of Graft-Versus-Host Skin Disease (GVHD) Fumi Miyagawa,

Cutaneous RANK–RANKL Signaling Upregulates CD8-Mediated Antiviral Immunity during Herpes simplex Virus Infection by Preventing Virus-Induced Langerhans.

Activated Kras Alters Epidermal Homeostasis of Mouse Skin, Resulting in Redundant Skin and Defective Hair Cycling Anandaroop Mukhopadhyay, Suguna R.

Gregory D. Rak, Lisa C. Osborne, Mark C. Siracusa, Brian S

Mesenchymal Stem Cells (MSCs) Attenuate Cutaneous Sclerodermatous Graft-Versus- Host Disease (Scl-GVHD) through Inhibition of Immune Cell Infiltration.

Volume 34, Issue 3, Pages (March 2011)

CXCR3-Mediated Skin Homing of Autoreactive CD8 T Cells Is a Key Determinant in Murine Graft-Versus-Host Disease Vadim A. Villarroel, Naoko Okiyama, Gaku.

Upregulation of Inflammatory Cytokines and Oncogenic Signal Pathways Preceding Tumor Formation in a Murine Model of T-Cell Lymphoma in Skin Xuesong Wu,

Kruppel-Like Factor KLF4 Facilitates Cutaneous Wound Healing by Promoting Fibrocyte Generation from Myeloid-Derived Suppressor Cells Lingling Ou, Ying.

Induction of Autoimmunity in a Bleomycin-Induced Murine Model of Experimental Systemic Sclerosis: An Important Role for CD4+ T Cells Hideaki Ishikawa,

Volume 13, Issue 6, Pages (November 2015)

Perivascular Hair Follicle Stem Cells Associate with a Venule Annulus

Volume 13, Issue 2, Pages (August 2013)

Shilpak Chatterjee, Jonathan M. Eby, Amir A

Characterization of Innate Lymphoid Cells in Human Skin and Blood Demonstrates Increase of NKp44+ ILC3 in Psoriasis Federica Villanova, Barry Flutter,

Protective Effect of Kit Signaling for Melanocyte Stem Cells against Radiation-Induced Genotoxic Stress Hitomi Aoki, Akira Hara, Tsutomu Motohashi, Takahiro.

Volume 142, Issue 2, Pages e2 (February 2012)

Hair Cycle Resting Phase Is Regulated by Cyclic Epithelial FGF18 Signaling Miho Kimura-Ueki, Yuko Oda, Junko Oki, Akiko Komi-Kuramochi, Emi Honda, Masahiro.

Γδ T Cells Augment Rejection of Skin Grafts by Enhancing Cross-Priming of CD8 T Cells to Skin-Derived Antigen Azad Rahimpour, Stephen R. Mattarollo,

Α-MSH-Stimulated Tolerogenic Dendritic Cells Induce Functional Regulatory T Cells and Ameliorate Ongoing Skin Inflammation Matteo Auriemma, Thomas Brzoska,

Transient CD44 Variant Isoform Expression and Reduction in CD4+/CD25+ Regulatory T Cells in C3H/HeJ Mice with Alopecia Areata Margot Zöller, Kevin J.

Wanglong Qiu, Xiaojun Li, Hongyan Tang, Alicia S. Huang, Andrey A

IL-23 from Langerhans Cells Is Required for the Development of Imiquimod-Induced Psoriasis-Like Dermatitis by Induction of IL-17A-Producing γδ T Cells

IL-10-Producing Langerhans Cells and Regulatory T Cells Are Responsible for Depressed Contact Hypersensitivity in Grafted Skin Ryutaro Yoshiki, Kenji.

Natural Killer T Cells Are Essential for the Development of Contact Hypersensitivity in BALB/c Mice Chihiro Shimizuhira, Atsushi Otsuka, Tetsuya Honda,

Transfer of Alopecia Areata to C3H/HeJ Mice Using Cultured Lymph Node–Derived Cells Eddy H.C. Wang, Mohsen Khosravi-Maharlooei, Reza Baradar Jalili,

B-1a and B-1b Cells Exhibit Distinct Developmental Requirements and Have Unique Functional Roles in Innate and Adaptive Immunity to S. pneumoniae Karen.

Absence of Cutaneous TNFα-Producing CD4+ T Cells and TNFα may Allow for Fibrosis Rather than Epithelial Cytotoxicity in Murine Sclerodermatous Graft-Versus-Host.

Disrupted Ectodermal Organ Morphogenesis in Mice with a Conditional Histone Deacetylase 1, 2 Deletion in the Epidermis Michael W. Hughes, Ting-Xin Jiang,

RANK Is Expressed in Metastatic Melanoma and Highly Upregulated on Melanoma- Initiating Cells Verena Kupas, Carsten Weishaupt, Dorothee Siepmann, Maria-Laura.

Transcription Factor CTIP2 Maintains Hair Follicle Stem Cell Pool and Contributes to Altered Expression of LHX2 and NFATC1 Shreya Bhattacharya, Heather.

Fuz Controls the Morphogenesis and Differentiation of Hair Follicles through the Formation of Primary Cilia Daisy Dai, Huiping Zhu, Bogdan Wlodarczyk,

Toshiyuki Yamamoto, Kiyoshi Nishioka

Integrin αE(CD103) Is Involved in Regulatory T-Cell Function in Allergic Contact Hypersensitivity Andrea Braun, Nadin Dewert, Fiona Brunnert, Viktor.

Antisense Targeting of cFLIP Sensitizes Activated T Cells to Undergo Apoptosis and Desensitizes Responses to Contact Dermatitis Dan V. Mourich, Jessica.

Functional Characterization of Melanocyte Stem Cells in Hair Follicles

The Temporal and Spatial Dynamics of Foxp3+ Treg Cell–Mediated Suppression during Contact Hypersensitivity Responses in a Murine Model Sari Lehtimäki,

Volume 27, Issue 3, Pages (September 2007)

Increased Severity of Bleomycin-Induced Skin Fibrosis in Mice with Leukocyte-Specific Protein 1 Deficiency JianFei Wang, Haiyan Jiao, Tara L. Stewart,

Murine Epidermal Label-Retaining Cells Isolated by Flow Cytometry do not Express the Stem Cell Markers CD34, Sca-1, or Flk-1 Michael R. Albert, Ruth-Ann.

Keratinocytes Function as Accessory Cells for Presentation of Endogenous Antigen Expressed in the Epidermis Brian S. Kim, Fumi Miyagawa, Young-Hun Cho,

Brile Chung, Eric Dudl, Akira Toyama, Lora Barsky, Kenneth I. Weinberg

Botulinum Neurotoxin A Decreases Infiltrating Cutaneous Lymphocytes and Improves Acanthosis in the KC-Tie2 Mouse Model Nicole L. Ward, Kevin D. Kavlick,

Transcutaneous Gene Gun Delivery of hNC16A Induces BPAG2-Specific Tolerance Monika Ettinger, Doris Peckl-Schmid, Christina Gruber, Martin Laimer, Josef.

Delineating Immune-Mediated Mechanisms Underlying Hair Follicle Destruction in the Mouse Mutant Defolliculated Fiona Ruge, Aikaterini Glavini, Awen M.

A Mouse Model of Vitiligo with Focused Epidermal Depigmentation Requires IFN-γ for Autoreactive CD8+ T-Cell Accumulation in the Skin John E. Harris,

Jaana Mannik, Kamil Alzayady, Soosan Ghazizadeh

T Cells with Low Avidity for a Tissue-Restricted Antigen Routinely Evade Central and Peripheral Tolerance and Cause Autoimmunity Dietmar Zehn, Michael.

Jonathan M. Eby, Hee-Kap Kang, Sean T. Tully, Wendy E

Ingenol Mebutate Field-Directed Treatment of UVB-Damaged Skin Reduces Lesion Formation and Removes Mutant p53 Patches Sarah-Jane Cozzi, Steven M. Ogbourne,

In Vivo Expansion of Regulatory T cells With IL-2/IL-2 mAb Complexes Prevents Anti- factor VIII Immune Responses in Hemophilia A Mice Treated With Factor.

Jennifer K. Broom, Andrew M. Lew, Hiroaki Azukizawa, Tony J

Volume 17, Issue 4, Pages (October 2002)

Transgenic Expression of Interleukin-13 in the Skin Induces a Pruritic Dermatitis and Skin Remodeling Tao Zheng, Min H. Oh, Sun Y. Oh, John T. Schroeder,

Herlina Y. Handoko, Neil F. Box, Graeme J. Walker

Volume 28, Issue 5, Pages (May 2008)

Volume 38, Issue 6, Pages (June 2013)

Bernice Y. Kwong, Scott J. Roberts, Tobias Silberzahn, Renata B

Partial Maintenance and Long-Term Expansion of Murine Skin Epithelial Stem Cells by Wnt-3a In Vitro Yukiteru Ouji, Shigeaki Ishizaka, Fukumi Nakamura-Uchiyama,

SOCS1 Prevents Potentially Skin-Reactive Cytotoxic T Lymphocytes from Gaining the Ability to Cause Inflammatory Lesions Galaxia Maria Rodriguez, Dante.

Volume 13, Issue 6, Pages (November 2015)

Skin-Infiltrating Monocytes/Macrophages Migrate to Draining Lymph Nodes and Produce IL-10 After Contact Sensitizer Exposure to UV-Irradiated Skin Eiko.

Volume 16, Issue 6, Pages (June 2002)

Errata Journal of Investigative Dermatology

Volume 37, Issue 2, Pages (August 2012)

UV Exposure Boosts Transcutaneous Immunization and Improves Tumor Immunity: Cytotoxic T-Cell Priming through the Skin Pamela Stein, Gerd Rechtsteiner,

Presentation transcript:

T-Cell Reconstitution after Thymus Xenotransplantation Induces Hair Depigmentation and Loss Anna L. Furmanski, Ryan F.L. O'Shaughnessy, Jose Ignacio Saldana, Michael P. Blundell, Adrian J. Thrasher, Neil J. Sebire, E. Graham Davies, Tessa Crompton Journal of Investigative Dermatology Volume 133, Issue 5, Pages 1221-1230 (May 2013) DOI: 10.1038/jid.2012.492 Copyright © 2013 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 1 De novo T-cell development in nude mice with human thymus xenografts. T-cell output following transplantation was assessed by flow cytometric analysis of peripheral blood lymphocytes (PBL). Control nudes received no graft; Wt/Nu are immunocompetent. (a) CD4+/CD8+ T cells identified by gating on PBL (B, NK, γδT, and dendritic cells were excluded). Example staining at 18 weeks post transplant is shown. (b) CD3 expression on CD4+ and CD8+ PBL. Example staining of (c) mouse PBL with anti-human antibodies, and of (d) human PBL with anti-human and anti-mouse antibodies. (e) Time-course analysis of % CD3+ T cells in blood. (f) % CD4+ and CD8+ cells as shown in a for four Nu-Tp mice. (g) Anti-mouse staining of normal mouse thymus and tissue retrieved from Nu-Tp transplantation site. Journal of Investigative Dermatology 2013 133, 1221-1230DOI: (10.1038/jid.2012.492) Copyright © 2013 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 2 Nude mice with functional thymus grafts develop profound hair loss. (a) Gross anatomy of control (left, pigmented) or Nu-Tp (right, depigmented) mice. (b) Loss of hair and thinning of Nu-Tp skin. Equivalent regions in Nu-Tp (c–f) and nude control (g–j) skin by hematoxylin and eosin histology. Pigmented hairs are seen in control nude skin but not in Nu-Tp skin. Arrows show immune infiltrates around (c) Nu-Tp and (g) control follicles. (k) Intact black/white hair follicles per field of view (FOV, n=15/sample at intervals through specimen, *P<0.0001) were quantified under low-power microscopy (see Supplementary Figure S2 online). Nude mean: 7.0±1.0, median: 7; Nu3 mean: 0.2±0.4, median: 0; Nu5 mean: 1.9±1.0, median: 2; Nu7 mean: 0.07±0.3, median: 0. (l) Digested dorsal skin samples analyzed by flow cytometry for skin-resident T cells. WT, wild type. Journal of Investigative Dermatology 2013 133, 1221-1230DOI: (10.1038/jid.2012.492) Copyright © 2013 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 3 Adoptive transfer of lymphocytes from Nu-Tp into hairy immunocompromized mice causes striking coat depigmentation. (a) Lymph node (LN) cells were injected intravenously into RAG−/- recipients (AT1). (b–e) Progressive coat depigmentation in AT1 mice. (f) Independent repeat of a. (g) Flow cytometric analysis of skin from wild type (WT) (immunocompetent) and black, white, and balding areas of AT1 RAG−/- mouse. Non-transferred and sham-transferred RAG−/- mice showed no skin phenotype (first/second mice from left in e) or T cells in blood (not shown). (h) Quantification of intact hair follicles per field of view (FOV) (*P<0.001, see Supplementary Figure S2 online). Control mean: 9.0±2.2, median: 8.5; AT1a left flank mean: 0.1±0.3, median: 0; AT1a right flank mean: 0.3±0.6, median: 0; AT1b left flank mean: 3.1±2.8, median: 3; AT1b right flank mean: 0, median: 0. Journal of Investigative Dermatology 2013 133, 1221-1230DOI: (10.1038/jid.2012.492) Copyright © 2013 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 4 T cells were observed in skin of RAG−/- AT1 mice with depigmentation. (a–d) Hematoxylin and eosin stain and histology of skin from AT1 RAG−/- mice and (e–h) controls; bars=100μm. Analysis of equivalent regions in AT1 and control skin during (a, b, e, f) anagen, (c, g) catagen, (d, h) and telogen. Arrows show cellular infiltrates around the follicular bulge region in (a) anagen and bulb in (d) telogen and equivalent locations in (e, h) control skin. (c, g: es) Catagen epithelial strands appear normal. (i, j) Immunofluorescent identification of CD4+ and CD8+ cells in skin of (i) Nu-Tp and nude control, and (j) AT1 Rag−/- and wild-type (WT) control mice. Control sections (no primary antibody) did not show staining (not shown). “h” on images denotes hair follicles. Journal of Investigative Dermatology 2013 133, 1221-1230DOI: (10.1038/jid.2012.492) Copyright © 2013 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 5 CD4+ cells alone from depigmented mice caused depigmentation and hair loss in further immunocompromised animals. (a) CD4+, CD8+, and γδTCR+ LN (lymph node) lymphocytes were sorted from AT1 RAG−/- depigmented mice by FACS and adoptively transferred into further RAG−/- recipients (AT2). (b) Purity of sorted populations confirmed by flow cytometry. (c) Receipt of CD4+ cells only caused areas of fur thinning, where the remaining hair was downy and depigmented. (d) The proportion of CD4+CD3hi cells was assessed in white and black areas of AT2-CD4 skin in comparison with wild-type (WT) control skin by flow cytometry. Journal of Investigative Dermatology 2013 133, 1221-1230DOI: (10.1038/jid.2012.492) Copyright © 2013 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 6 Melanocyte-lineage cells are decreased in Nu-Tp skin, and Nu-Tp T cells activate in response to syngeneic melanocytes. (a) Trp2 staining in hair bulbs of control and Nu-Tp (Nu5), coincident with regions containing melanocytes/melanosomes, as shown in the companion bright-field view. Note the reduction of Trp2 staining in the remaining black hairs in the Nu5-transplanted mouse. Dotted lines denote the dermal papilla–matrix boundary. Bar=50μm. (b) The expression of CD25 (T-cell activation marker) on CD4+ cells from Nu-Tp spleen or CD4+ B6 splenocytes after 48hours of exposure to syngeneic B6 melanocytes (irradiated melan-a). (c) The proportion of effector memory CD4+ cells (CD4+CD44hiCD62Llo) and naive (CD4+CD62L+CD44lo) cells in Nu-Tp spleen+B6 melanocyte cocultures compared with B6 spleen+B6 melanocyte cocultures. WT, wild type. Journal of Investigative Dermatology 2013 133, 1221-1230DOI: (10.1038/jid.2012.492) Copyright © 2013 The Society for Investigative Dermatology, Inc Terms and Conditions