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Article ; Online: Skin barrier immunity and ageing.

Chambers, Emma S / Vukmanovic-Stejic, Milica

2019 Volume 160, Issue 2, Page(s) 116–125

Abstract: The skin is the outermost layer of the body with an extensive surface area of approximately 1·8 m ...

Abstract	The skin is the outermost layer of the body with an extensive surface area of approximately 1·8 m
MeSH term(s)	Adipocytes/immunology ; Aging/immunology ; Disease Susceptibility ; Fibroblasts/immunology ; Humans ; Immunity, Cellular ; Incidence ; Keratinocytes/immunology ; Langerhans Cells/immunology ; Macrophages/immunology ; Microbiota/immunology ; Skin/cytology ; Skin/immunology ; Skin/microbiology ; Skin Diseases, Infectious/epidemiology ; Skin Diseases, Infectious/immunology ; Skin Diseases, Infectious/microbiology ; Skin Neoplasms/epidemiology ; Skin Neoplasms/immunology ; Water Loss, Insensible/immunology
Language	English
Publishing date	2019-12-04
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	80124-0
ISSN	1365-2567 ; 0019-2805 ; 0953-4954
ISSN (online)	1365-2567
ISSN	0019-2805 ; 0953-4954
DOI	10.1111/imm.13152
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Article: CD4 T-Cell Dysregulation in Psoriatic Arthritis Reveals a Regulatory Role for IL-22.

Ezeonyeji, Amara / Baldwin, Helen / Vukmanovic-Stejic, Milica / Ehrenstein, Michael R

Frontiers in immunology

2017 Volume 8, Page(s) 1403

Abstract: Dysregulation of interleukin-22 (IL-22) has been associated with autoimmune diseases but divergent effects upon inflammation have hampered efforts to define its contribution to pathogenesis. Here, we examined the role of IL-22 in patients with psoriatic ... ...

Abstract	Dysregulation of interleukin-22 (IL-22) has been associated with autoimmune diseases but divergent effects upon inflammation have hampered efforts to define its contribution to pathogenesis. Here, we examined the role of IL-22 in patients with psoriatic arthritis (PsA). In the peripheral blood of PsA patients, there was a decrease in IL-22
Language	English
Publishing date	2017-10-27
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2606827-8
ISSN	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2017.01403
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Article ; Online: Recruitment of inflammatory monocytes by senescent fibroblasts inhibits antigen-specific tissue immunity during human aging.

Chambers, Emma S / Vukmanovic-Stejic, Milica / Shih, Barbara B / Trahair, Hugh / Subramanian, Priya / Devine, Oliver P / Glanville, James / Gilroy, Derek / Rustin, Malcolm H A / Freeman, Tom C / Mabbott, Neil A / Akbar, Arne N

Nature aging

2021 Volume 1, Issue 1, Page(s) 101–113

Abstract: We have previously shown that healthy older adults exhibit reduced cutaneous immune responses during a varicella zoster virus (VZV) antigen challenge that correlated with a nonspecific inflammatory response to the injection itself. Here we found that ... ...

Abstract	We have previously shown that healthy older adults exhibit reduced cutaneous immune responses during a varicella zoster virus (VZV) antigen challenge that correlated with a nonspecific inflammatory response to the injection itself. Here we found that needle damage during intradermal injections in older adults led to an increase in the number of cutaneous senescent fibroblasts expressing CCL2, resulting in the local recruitment of inflammatory monocytes. These infiltrating monocytes secreted prostaglandin E2, which inhibited resident memory T cell activation and proliferation. Pretreatment of older participants with a p38 mitogen-activated protein kinase inhibitor in vivo decreased CCL2 expression and inhibited monocyte recruitment and secretion of prostaglandin E2. This coincided with an increased response to VZV antigen challenge in the skin. Our results point to a series of molecular and cellular mechanisms that link cellular senescence, tissue damage, excessive inflammation and reduced immune responsiveness in human skin and demonstrate that tissue-specific immunity can be restored in older adults by short-term inhibition of inflammatory responses.
MeSH term(s)	Humans ; Aged ; Monocytes ; Dinoprostone/metabolism ; Aging ; Herpesvirus 3, Human ; Lymphocyte Activation ; Fibroblasts
Chemical Substances	Dinoprostone (K7Q1JQR04M)
Language	English
Publishing date	2021-01-14
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2662-8465
ISSN (online)	2662-8465
DOI	10.1038/s43587-020-00010-6
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Article ; Online: A Suction Blister Protocol to Study Human T-cell Recall Responses In Vivo.

Holm, Line L / Vukmanovic-Stejic, Milica / Blauenfeldt, Thomas / Benfield, Thomas / Andersen, Peter / Akbar, Arne N / Ruhwald, Morten

Journal of visualized experiments : JoVE

2018 , Issue 138

Abstract: Cutaneous antigen-recall models allow for studies of human memory responses in vivo. When combined with skin suction blister (SB) induction, this model offers accessibility to rare populations of antigen-specific T-cells representative of the cellular ... ...

Abstract	Cutaneous antigen-recall models allow for studies of human memory responses in vivo. When combined with skin suction blister (SB) induction, this model offers accessibility to rare populations of antigen-specific T-cells representative of the cellular memory response as well as the cytokine microenvironment in situ. This report describes the practical procedure of a cutaneous recall, an SB induction, and a harvest of antigen-specific T-cells. To exemplify the method, the tuberculin skin test is used for antigenic recall in individuals who, prior to this study, underwent a Bacillus Calmette-Guérin vaccination against an infection with Mycobacterium tuberculosis. Finally, examples of multiplex and flow cytometric analyses of SB specimens are provided, illustrating high fractions of antigen-specific polyfunctional CD4+ T-cells available by this sampling method compared with cells isolated from the blood. The method described here is safe and minimally invasive, provides a unique opportunity to study both innate and adaptive immune responses in vivo, and may be beneficial to a broad community of researchers working with cell-mediated immunity and human memory responses, in the context of vaccine development.
MeSH term(s)	BCG Vaccine/pharmacology ; BCG Vaccine/therapeutic use ; Blister/etiology ; Humans ; Immunity, Cellular/immunology ; Mycobacterium tuberculosis/pathogenicity ; Skin/immunology ; T-Lymphocytes/immunology ; Tuberculosis/diagnosis ; Tuberculosis/immunology
Chemical Substances	BCG Vaccine
Language	English
Publishing date	2018-08-11
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Video-Audio Media
ISSN	1940-087X
ISSN (online)	1940-087X
DOI	10.3791/57554
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Article ; Online: Vitamin D

Chambers, Emma S / Vukmanovic-Stejic, Milica / Turner, Carolin T / Shih, Barbara B / Trahair, Hugh / Pollara, Gabriele / Tsaliki, Evdokia / Rustin, Malcolm / Freeman, Tom C / Mabbott, Neil A / Noursadeghi, Mahdad / Martineau, Adrian R / Akbar, Arne N

Immunotherapy advances

2020 Volume 1, Issue 1, Page(s) ltaa008

Abstract: Introduction: Ageing is associated with increased number of infections, decreased vaccine efficacy and increased systemic inflammation termed inflammageing. These changes are reflected by reduced recall responses to varicella zoster virus (VZV) ... ...

Abstract	Introduction: Ageing is associated with increased number of infections, decreased vaccine efficacy and increased systemic inflammation termed inflammageing. These changes are reflected by reduced recall responses to varicella zoster virus (VZV) challenge in the skin of older adults. Vitamin D deficiency is more common in the old and has been associated with frailty and increased inflammation. In addition, vitamin D increases immunoregulatory mechanisms and therefore has the potential to inhibit inflammageing. Objectives: We investigated the use of vitamin D Methods: Vitamin D insufficient older adults ( Results: We showed that older adults had reduced VZV-specific cutaneous immune response and increased non-specific inflammation as compared to young. Increased non-specific inflammation observed in the skin of older adults negatively correlated with vitamin D sufficiency. We showed that vitamin D Conclusion: Vitamin D
Language	English
Publishing date	2020-11-25
Publishing country	England
Document type	Journal Article
ISSN	2732-4303
ISSN (online)	2732-4303
DOI	10.1093/immadv/ltaa008
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Article ; Online: Compartmentalized cytotoxic immune response leads to distinct pathogenic roles of natural killer and senescent CD8

Covre, Luciana Polaco / Devine, Oliver Patrick / Garcia de Moura, Renan / Vukmanovic-Stejic, Milica / Dietze, Reynaldo / Ribeiro-Rodrigues, Rodrigo / Guedes, Herbert Leonel de Matos / Lubiana Zanotti, Raphael / Falqueto, Aloisio / Akbar, Arne N / Gomes, Daniel Claudio Oliveira

Immunology

2020 Volume 159, Issue 4, Page(s) 429–440

Abstract: Cytotoxic activity mediated by ... ...

Abstract	Cytotoxic activity mediated by CD8
MeSH term(s)	CD56 Antigen/genetics ; CD56 Antigen/immunology ; CD57 Antigens/genetics ; CD57 Antigens/immunology ; Case-Control Studies ; Cellular Senescence/immunology ; Cytotoxicity, Immunologic ; Female ; Gene Expression Regulation ; Host-Parasite Interactions/genetics ; Host-Parasite Interactions/immunology ; Humans ; Interferon-gamma/genetics ; Interferon-gamma/immunology ; Killer Cells, Natural/immunology ; Killer Cells, Natural/parasitology ; Killer Cells, Natural/pathology ; Lectins, C-Type/genetics ; Lectins, C-Type/immunology ; Leishmania braziliensis/immunology ; Leishmania braziliensis/pathogenicity ; Leishmaniasis, Cutaneous/immunology ; Leishmaniasis, Cutaneous/parasitology ; Leishmaniasis, Cutaneous/pathology ; Male ; Oligosaccharides/genetics ; Oligosaccharides/immunology ; Receptors, Immunologic/genetics ; Receptors, Immunologic/immunology ; Severity of Illness Index ; Sialyl Lewis X Antigen/analogs & derivatives ; Sialyl Lewis X Antigen/genetics ; Sialyl Lewis X Antigen/immunology ; Signal Transduction ; Skin/immunology ; Skin/parasitology ; Skin/pathology ; T-Lymphocytes, Cytotoxic/immunology ; T-Lymphocytes, Cytotoxic/parasitology ; T-Lymphocytes, Cytotoxic/pathology
Chemical Substances	6-sulfo sialyl Lewis X ; CD56 Antigen ; CD57 Antigens ; KLRG1 protein, human ; Lectins, C-Type ; NCAM1 protein, human ; Oligosaccharides ; Receptors, Immunologic ; Sialyl Lewis X Antigen ; Interferon-gamma (82115-62-6)
Language	English
Publishing date	2020-01-26
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80124-0
ISSN	1365-2567 ; 0019-2805 ; 0953-4954
ISSN (online)	1365-2567
ISSN	0019-2805 ; 0953-4954
DOI	10.1111/imm.13173
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Article ; Online: Circulating Senescent T Cells Are Linked to Systemic Inflammation and Lesion Size During Human Cutaneous Leishmaniasis.

Covre, Luciana P / Martins, Régia F / Devine, Oliver P / Chambers, Emma S / Vukmanovic-Stejic, Milica / Silva, Juliana A / Dietze, Reynaldo / Rodrigues, Rodrigo R / de Matos Guedes, Herbert L / Falqueto, Aloísio / Akbar, Arne N / Gomes, Daniel C O

Frontiers in immunology

2019 Volume 9, Page(s) 3001

Abstract: Leishmania (Viannia) ... ...

Abstract	Leishmania (Viannia) braziliensis
MeSH term(s)	Adult ; Cellular Senescence/immunology ; Cytokines/immunology ; Cytokines/metabolism ; Female ; Humans ; Inflammation/blood ; Inflammation/immunology ; Leishmania braziliensis/immunology ; Leishmaniasis, Cutaneous/blood ; Leishmaniasis, Cutaneous/immunology ; Leishmaniasis, Cutaneous/parasitology ; Leishmaniasis, Cutaneous/pathology ; Male ; Middle Aged ; Receptors, Lymphocyte Homing/immunology ; Receptors, Lymphocyte Homing/metabolism ; Skin/immunology ; Skin/parasitology ; Skin/pathology ; T-Lymphocytes/immunology ; T-Lymphocytes/metabolism ; Young Adult
Chemical Substances	Cytokines ; Receptors, Lymphocyte Homing
Language	English
Publishing date	2019-01-04
Publishing country	Switzerland
Document type	Journal Article ; Observational Study ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2018.03001
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Article ; Online: Measurement of proliferation and disappearance of regulatory T cells in human studies using deuterium-labeled glucose.

Vukmanovic-Stejic, Milica / Zhang, Yan / Akbar, Arne N / Macallan, Derek C

Methods in molecular biology (Clifton, N.J.)

2011 Volume 707, Page(s) 243–261

Abstract: The in vivo proliferation and disappearance kinetics of lymphocytes may be estimated in humans from rates of deuterium-labeled glucose ((2)H(2)-glucose) incorporation into DNA. This protocol describes its application to regulatory T cells (Treg). Because ...

Abstract	The in vivo proliferation and disappearance kinetics of lymphocytes may be estimated in humans from rates of deuterium-labeled glucose ((2)H(2)-glucose) incorporation into DNA. This protocol describes its application to regulatory T cells (Treg). Because Treg divide frequently, (2)H(2)-glucose is a suitable precursor, achieving high levels of enrichment over a short period. Being nonradioactive and readily administered, it is appropriate for human studies.There are four phases to the method: labeling, sampling, analysis and modeling. Labeling consists of administration of (2)H(2)-glucose, either intravenously or orally; during this phase, small blood samples are taken to monitor plasma glucose enrichment. Sampling occurs over the ensuing ∼3 weeks; PBMC are collected and sorted according to surface marker expression. Cell separation can be achieved by fluorescence-activated cell sorting (FACS) using CD4, CD45RA and CD25 to define memory Treg (CD4(+)CD25(hi)), or by a combination of magnetic bead separation and FACS. Analysis consists of DNA extraction, hydrolysis, derivatization to the pentafluoro tri-acetate (PFTA) derivative, and quantitation of deuterium content by gas-chromatography mass-spectrometry (GC/MS). The ratio of deuterium enrichment in cellular DNA relative to plasma glucose is used to derive the fraction of new cells in the sorted population, and this is modeled as a function of time to derive proliferation and disappearance kinetics.
MeSH term(s)	Cell Proliferation ; Deuterium/metabolism ; Glucose/metabolism ; Humans ; Isotope Labeling/methods ; Models, Biological ; T-Lymphocytes, Regulatory/cytology
Chemical Substances	Deuterium (AR09D82C7G) ; Glucose (IY9XDZ35W2)
Language	English
Publishing date	2011-02-02
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-61737-979-6_16
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Article ; Online: Skin resident memory CD8

Seidel, J A / Vukmanovic-Stejic, M / Muller-Durovic, B / Patel, N / Fuentes-Duculan, J / Henson, S M / Krueger, J G / Rustin, M H A / Nestle, F O / Lacy, K E / Akbar, A N

Clinical and experimental immunology

2018 Volume 194, Issue 1, Page(s) 79–92

Abstract: The in-depth understanding of skin resident memory ... ...

Abstract	The in-depth understanding of skin resident memory CD8
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Antigens, CD/metabolism ; Antigens, Differentiation, T-Lymphocyte/metabolism ; CD28 Antigens/immunology ; CD57 Antigens/metabolism ; Cells, Cultured ; Female ; Granzymes/metabolism ; Humans ; Immunologic Memory/immunology ; Interleukin-15/immunology ; Interleukin-2/immunology ; Lectins, C-Type/metabolism ; Leukocyte Common Antigens/metabolism ; Male ; Middle Aged ; Perforin/metabolism ; Receptors, Immunologic ; Skin/cytology ; Skin/immunology ; T-Lymphocytes, Cytotoxic/immunology ; Trans-Activators/metabolism ; Tumor Necrosis Factor Receptor Superfamily, Member 7/metabolism ; Tumor Necrosis Factor-alpha/immunology ; Young Adult
Chemical Substances	Antigens, CD ; Antigens, Differentiation, T-Lymphocyte ; CD28 Antigens ; CD57 Antigens ; CD69 antigen ; IL15 protein, human ; IL2 protein, human ; Interleukin-15 ; Interleukin-2 ; KLRG1 protein, human ; Lectins, C-Type ; Receptors, Immunologic ; Trans-Activators ; Tumor Necrosis Factor Receptor Superfamily, Member 7 ; Tumor Necrosis Factor-alpha ; Perforin (126465-35-8) ; Leukocyte Common Antigens (EC 3.1.3.48) ; Granzymes (EC 3.4.21.-)
Language	English
Publishing date	2018-09-12
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	218531-3
ISSN	1365-2249 ; 0009-9104 ; 0964-2536
ISSN (online)	1365-2249
ISSN	0009-9104 ; 0964-2536
DOI	10.1111/cei.13189
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Article ; Online: Impact of Zostavax Vaccination on T-Cell Accumulation and Cutaneous Gene Expression in the Skin of Older Humans After Varicella Zoster Virus Antigen-Specific Challenge.

Patel, Neil P / Vukmanovic-Stejic, Milica / Suarez-Farinas, Mayte / Chambers, Emma S / Sandhu, Daisy / Fuentes-Duculan, Judilyn / Mabbott, Neil A / Rustin, Malcolm H A / Krueger, James / Akbar, Arne N

The Journal of infectious diseases

2018 Volume 218, Issue suppl_2, Page(s) S88–S98

Abstract: Background: The live attenuated vaccine Zostavax was developed to prevent varicella zoster virus (VZV) reactivation that causes herpes zoster (shingles) in older humans. However, the impact of vaccination on the cutaneous response to VZV is not known.!## ...

Abstract	Background: The live attenuated vaccine Zostavax was developed to prevent varicella zoster virus (VZV) reactivation that causes herpes zoster (shingles) in older humans. However, the impact of vaccination on the cutaneous response to VZV is not known. Methods: We investigated the response to intradermal VZV antigen challenge before and after Zostavax vaccination in participants >70 years of age by immunohistological and transcriptomic analyses of skin biopsy specimens collected from the challenge site. Results: Vaccination increased the proportion of VZV-specific CD4+ T cells in the blood and promoted the accumulation of both CD4+ and CD8+ T cells in the skin after VZV antigen challenge. However, Zostavax did not alter the proportion of resident memory T cells (CD4+ and CD8+) or CD4+Foxp3+ regulatory T cells in unchallenged skin. After vaccination, there was increased cutaneous T-cell proliferation at the challenge site and also increased recruitment of T cells from the blood, as indicated by an elevated T-cell migratory gene signature. CD8+ T-cell-associated functional genes were also highly induced in the skin after vaccination. Conclusion: Zostavax vaccination does not alter the abundance of cutaneous resident memory T cells but instead increases the recruitment of VZV-specific T cells from the blood and enhances T-cell activation, particularly cells of the CD8+ subset, in the skin after VZV antigen challenge.
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Antigens, Viral/immunology ; CD4-Positive T-Lymphocytes/physiology ; Cohort Studies ; Female ; Gene Expression Regulation/immunology ; Herpes Zoster/prevention & control ; Herpes Zoster Vaccine/immunology ; Herpesvirus 3, Human/immunology ; Humans ; Lymphocyte Activation ; Male ; T-Lymphocyte Subsets/physiology ; T-Lymphocytes, Regulatory/physiology ; Vaccination ; Vaccines, Attenuated/immunology ; Young Adult
Chemical Substances	Antigens, Viral ; Herpes Zoster Vaccine ; Vaccines, Attenuated
Language	English
Publishing date	2018-10-23
Publishing country	United States
Document type	Clinical Trial ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3019-3
ISSN	1537-6613 ; 0022-1899
ISSN (online)	1537-6613
ISSN	0022-1899
DOI	10.1093/infdis/jiy420
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