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Article ; Online: IL-36: a therapeutic target for ulcerative colitis?

Hernandez Santana, Yasmina E / Irwin, Naoise / Walsh, Patrick T

2022 Volume 26, Issue 6, Page(s) 507–512

MeSH term(s)	Colitis, Ulcerative/drug therapy ; Crohn Disease ; Humans
Language	English
Publishing date	2022-06-02
Publishing country	England
Document type	Editorial ; Research Support, Non-U.S. Gov't
ZDB-ID	2055208-7
ISSN	1744-7631 ; 1472-8222
ISSN (online)	1744-7631
ISSN	1472-8222
DOI	10.1080/14728222.2022.2084381
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Zs.A 5244: Show issues

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Article ; Online: Interleukin-1 family cytokines at the crossroads of microbiome regulation in barrier health and disease.

Narros-Fernández, Paloma / Chomanahalli Basavarajappa, Shrikanth / Walsh, Patrick T

The FEBS journal

2023 Volume 291, Issue 9, Page(s) 1849–1869

Abstract: Recent advances in understanding how the microbiome can influence both the physiology and the pathogenesis of disease in humans have highlighted the importance of gaining a deeper insight into the complexities of the host-microbial dialogue. In tandem ... ...

Abstract	Recent advances in understanding how the microbiome can influence both the physiology and the pathogenesis of disease in humans have highlighted the importance of gaining a deeper insight into the complexities of the host-microbial dialogue. In tandem with this progress, has been a greater understanding of the biological pathways which regulate both homeostasis and inflammation at barrier tissue sites, such as the skin and the gut. In this regard, the Interleukin-1 family of cytokines, which can be segregated into IL-1, IL-18 and IL-36 subfamilies, have emerged as important custodians of barrier health and immunity. With established roles as orchestrators of various inflammatory diseases in both the skin and intestine, it is now becoming clear that IL-1 family cytokine activity is not only directly influenced by external microbes, but can also play important roles in shaping the composition of the microbiome at barrier sites. This review explores the current knowledge surrounding the evidence that places these cytokines as key mediators at the interface between the microbiome and human health and disease at the skin and intestinal barrier tissues.
MeSH term(s)	Humans ; Interleukin-1/metabolism ; Interleukin-1/immunology ; Interleukin-1/genetics ; Microbiota/immunology ; Skin/microbiology ; Skin/immunology ; Skin/metabolism ; Gastrointestinal Microbiome/immunology ; Animals ; Inflammation/microbiology ; Inflammation/metabolism ; Inflammation/immunology ; Homeostasis ; Intestinal Mucosa/microbiology ; Intestinal Mucosa/immunology ; Intestinal Mucosa/metabolism
Chemical Substances	Interleukin-1
Language	English
Publishing date	2023-06-18
Publishing country	England
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2173655-8
ISSN	1742-4658 ; 1742-464X
ISSN (online)	1742-4658
ISSN	1742-464X
DOI	10.1111/febs.16888
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Article ; Online: IFNγ is a central node of cancer immune equilibrium.

Walsh, Michael J / Stump, Courtney T / Kureshi, Rakeeb / Lenehan, Patrick / Ali, Lestat R / Dougan, Michael / Knipe, David M / Dougan, Stephanie K

Cell reports

2023 Volume 42, Issue 3, Page(s) 112219

Abstract: Tumors in immune equilibrium are held in balance between outgrowth and destruction by the immune system. The equilibrium phase defines the duration of clinical remission and stable disease, and escape from equilibrium remains a major clinical problem. ... ...

Abstract	Tumors in immune equilibrium are held in balance between outgrowth and destruction by the immune system. The equilibrium phase defines the duration of clinical remission and stable disease, and escape from equilibrium remains a major clinical problem. Using a non-replicating HSV-1 vector expressing interleukin-12 (d106S-IL12), we developed a mouse model of therapy-induced immune equilibrium, a phenomenon previously seen only in humans. This immune equilibrium was centrally reliant on interferon-γ (IFNγ). CD8
MeSH term(s)	Animals ; Humans ; Mice ; CD8-Positive T-Lymphocytes ; Interferon-gamma/metabolism ; Interleukin-12/metabolism ; Neoplasms ; Perforin
Chemical Substances	Interferon-gamma (82115-62-6) ; Interleukin-12 (187348-17-0) ; Perforin (126465-35-8) ; IFNG protein, mouse
Language	English
Publishing date	2023-03-06
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	2649101-1
ISSN	2211-1247 ; 2211-1247
ISSN (online)	2211-1247
ISSN	2211-1247
DOI	10.1016/j.celrep.2023.112219
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Article ; Online: The Diverse Roles of the IL-36 Family in Gastrointestinal Inflammation and Resolution.

Leon, Gemma / Hussey, Seamus / Walsh, Patrick T

Inflammatory bowel diseases

2020 Volume 27, Issue 3, Page(s) 440–450

Abstract: The interleukin (IL)-36 family is a member of the IL-1 superfamily of cytokines and, in common with other IL-1 family members, has been shown to exhibit pleiotropic effects in homeostasis and inflammation. Although the important role these cytokines play ...

Abstract	The interleukin (IL)-36 family is a member of the IL-1 superfamily of cytokines and, in common with other IL-1 family members, has been shown to exhibit pleiotropic effects in homeostasis and inflammation. Although the important role these cytokines play in the skin has been widely reported, recent evidence suggests that IL-36 family members are expressed and can also exert significant influence at the intestinal mucosa. In this review, we summarize current knowledge surrounding the role of the IL-36 in the intestines. In particular, we examine its likely dichotomous role as a mediator of both inflammation and resolution, highlighting its overlapping roles in innate and adaptive inflammation at the mucosa and its contribution to pathophysiology of inflammatory bowel disease. We also summarize the complexities of targeting this cytokine family in a clinical setting.
MeSH term(s)	Humans ; Inflammation ; Inflammatory Bowel Diseases/immunology ; Interleukin-1/immunology ; Intestinal Mucosa
Chemical Substances	Interleukin-1 ; interleukin 36, human
Language	English
Publishing date	2020-09-08
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1340971-2
ISSN	1536-4844 ; 1078-0998
ISSN (online)	1536-4844
ISSN	1078-0998
DOI	10.1093/ibd/izaa232
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Article ; Online: The IL-1 cytokine family as custodians of barrier immunity.

Matarazzo, Laura / Hernandez Santana, Yasmina E / Walsh, Patrick T / Fallon, Padraic G

Cytokine

2022 Volume 154, Page(s) 155890

Abstract: The interleukin-1 (IL-1) family of cytokines and receptors are implicated in the functioning of innate and adaptive immunity and the genesis of inflammation. They are widely expressed in structural and immune cells with marked expression within barrier ... ...

Abstract	The interleukin-1 (IL-1) family of cytokines and receptors are implicated in the functioning of innate and adaptive immunity and the genesis of inflammation. They are widely expressed in structural and immune cells with marked expression within barrier mucosal surfaces. In the lung, gut and skin, which are common entry sites for pathogens, they play essential functions in maintaining the functional integrity of the barrier and manage innate and adaptive immunity in response to insult and infections. In tissue sites, the IL-1 cytokines are tightly regulated by mechanisms involving decoy receptors and protease degradation. Dysregulation of these processes are associated with aberrant tissue inflammation leading to a number of inflammatory diseases. This review will address the roles of the different IL-1 cytokines at the lung, gut and skin barrier surfaces at homeostasis, and their roles as inflammatory mediators in diseases such as asthma, chronic obstructive pulmonary disease, inflammatory bowel diseases, atopic dermatitis and psoriasis.
MeSH term(s)	Adaptive Immunity ; Cytokines ; Humans ; Immunity, Innate ; Inflammation ; Inflammatory Bowel Diseases ; Interleukin-1
Chemical Substances	Cytokines ; Interleukin-1
Language	English
Publishing date	2022-04-21
Publishing country	England
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	1018055-2
ISSN	1096-0023 ; 1043-4666
ISSN (online)	1096-0023
ISSN	1043-4666
DOI	10.1016/j.cyto.2022.155890
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Zs.A 2840: Show issues

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Article ; Online: Blockade of innate inflammatory cytokines TNF

Walsh, Michael J / Ali, Lestat R / Lenehan, Patrick / Kureshi, Courtney T / Kureshi, Rakeeb / Dougan, Michael / Knipe, David M / Dougan, Stephanie K

Immunotherapy advances

2023 Volume 3, Issue 1, Page(s) ltad011

Abstract: Cancer therapeutics can lead to immune equilibrium in which the immune response controls tumor cell expansion without fully eliminating the cancer. The factors involved in this equilibrium remain incompletely understood, especially those that would ... ...

Abstract	Cancer therapeutics can lead to immune equilibrium in which the immune response controls tumor cell expansion without fully eliminating the cancer. The factors involved in this equilibrium remain incompletely understood, especially those that would antagonize the anti-tumor immune response and lead to tumor outgrowth. We previously demonstrated that continuous treatment with a non-replicating herpes simplex virus 1 expressing interleukin (IL)-12 induces a state of cancer immune equilibrium highly dependent on interferon-γ. We profiled the IL-12 virotherapy-induced immune equilibrium in murine melanoma, identifying blockade of innate inflammatory cytokines, tumor necrosis factor alpha (TNFα), IL-1β, or IL-6 as possible synergistic interventions. Antibody depletions of each of these cytokines enhanced survival in mice treated with IL-12 virotherapy and helped to overcome equilibrium in some tumors. Single-cell RNA-sequencing demonstrated that blockade of inflammatory cytokines resulted in downregulation of overlapping inflammatory pathways in macrophages, shifting immune equilibrium towards tumor clearance, and raising the possibility that TNFα blockade could synergize with existing cancer immunotherapies.
Language	English
Publishing date	2023-07-03
Publishing country	England
Document type	Journal Article
ISSN	2732-4303
ISSN (online)	2732-4303
DOI	10.1093/immadv/ltad011
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Article ; Online: Serum IL-36β levels are associated with Insulin sensitivity in paediatric patients with obesity.

Narros-Fernández, Paloma / O'Donnell, Andrew / Sheehy, Clodagh / Basavarajappa, Shrikanth Chomanahalli / Hernandez Santana, Yasmina Esther / Kinlen, David / Cody, Declan / Hogan, Andrew E / Walsh, Patrick T

International journal of obesity (2005)

2024

Abstract: Although the orchestrating role of Interleukin-36 cytokines in regulating inflammation at barrier tissue sites, is well established, whether they play a significant role in the settings of metabolic health and disease, has yet to be fully established. ... ...

Abstract	Although the orchestrating role of Interleukin-36 cytokines in regulating inflammation at barrier tissue sites, is well established, whether they play a significant role in the settings of metabolic health and disease, has yet to be fully established. Several recent studies have demonstrated that IL-36 cytokine expression is elevated among adult patients with obesity, and can play roles in regulating both insulin sensitivity and driving inflammation. In this report, we have extended these analyses to paediatric patients and identified an association between elevated serum levels of expression of the specific Interleukin-36 subfamily member, IL-36β, among children with obesity displaying insulin sensitivity, compared to children with obesity who are insulin resistant. While these data further indicate a possible protective role for IL-36 in metabolic health, they also differ with previous findings from an adult patient cohort, where elevated levels of the related cytokine, IL-36γ, were found to occur in association with improved metabolic health. While highlighting important differences between paediatric and adult patient cohorts in the context of metabolic disease associated with obesity, these data underscore the need for a deeper mechanistic analysis of the role of IL-36 cytokines in disease.
Language	English
Publishing date	2024-03-11
Publishing country	England
Document type	Journal Article
ZDB-ID	752409-2
ISSN	1476-5497 ; 0307-0565
ISSN (online)	1476-5497
ISSN	0307-0565
DOI	10.1038/s41366-024-01508-4
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Article: Opportunities to Target T Cell Trafficking in Pediatric Inflammatory Bowel Disease.

Giannoudaki, Eirini / Gargan, Siobhan / Hussey, Seamus / Long, Aideen / Walsh, Patrick T

Frontiers in pediatrics

2021 Volume 9, Page(s) 640497

Abstract: T cell subsets are considered central orchestrators of inflammation and homeostasis ... aimed at the neutralization of T cell effector cytokines have provided significant benefits ... for pediatric and adult patients, more recent strategies aimed at inhibiting the infiltration of pathogenic T ...

Abstract	T cell subsets are considered central orchestrators of inflammation and homeostasis in the intestine and are established targets for the treatment of inflammatory bowel disease. While approaches aimed at the neutralization of T cell effector cytokines have provided significant benefits for pediatric and adult patients, more recent strategies aimed at inhibiting the infiltration of pathogenic T cell subsets have also emerged. In this review, we describe current knowledge surrounding the function of T cell subsets in pediatric inflammatory bowel disease and outline approaches aimed at targeting T cell trafficking to the intestine which may represent a new treatment option for pediatric inflammatory bowel disease.
Language	English
Publishing date	2021-03-18
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2711999-3
ISSN	2296-2360
ISSN	2296-2360
DOI	10.3389/fped.2021.640497
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Article ; Online: Role of Molecular Layering in the Enhanced Mechanical Properties of Stable Glasses.

Wolf, Sarah E / Fulco, Sage / Zhang, Aixi / Zhao, Haoqiang / Walsh, Patrick J / Turner, Kevin T / Fakhraai, Zahra

The journal of physical chemistry letters

2022 Volume 13, Issue 15, Page(s) 3360–3368

Abstract: The density, degree of molecular orientation, and molecular layering of vapor-deposited stable glasses (SGs) vary with substrate temperature ( ...

Abstract	The density, degree of molecular orientation, and molecular layering of vapor-deposited stable glasses (SGs) vary with substrate temperature (
Language	English
Publishing date	2022-04-11
Publishing country	United States
Document type	Journal Article
ISSN	1948-7185
ISSN (online)	1948-7185
DOI	10.1021/acs.jpclett.2c00232
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Article ; Online: The emergence of the IL-36 cytokine family as novel targets for inflammatory diseases.

Walsh, Patrick T / Fallon, Padraic G

Annals of the New York Academy of Sciences

2016 Volume 1417, Issue 1, Page(s) 23–34

Abstract: The recently discovered interleukin (IL)-36 family of cytokines form part of the broader IL-1 family and are emerging as important mediators of inflammatory disease. The IL-36 subfamily consists of three ligands-IL-36α, IL-36β, and IL-36γ-and the natural ...

Abstract	The recently discovered interleukin (IL)-36 family of cytokines form part of the broader IL-1 family and are emerging as important mediators of inflammatory disease. The IL-36 subfamily consists of three ligands-IL-36α, IL-36β, and IL-36γ-and the natural antagonist IL-36Ra. The cytokines exert their effects through a specific IL-36 receptor consisting of IL-36R and IL-1RAcP chains. IL-36 cytokines can direct both innate and adaptive immune responses by acting on parenchymal, stromal, and specific immune cell subsets. In humans, inactivating mutations in the gene encoding the IL-36R antagonist, which lead to unregulated IL-36R signaling, lead to an autoinflammatory condition termed deficiency of the IL-36R antagonist, which primarily manifests as a severe form of pustular psoriasis. While such discoveries have prompted deeper mechanistic studies highlighting the important role of IL-36 cytokines in psoriatic skin inflammation, it is now evident that IL-36 cytokines can also play important roles in inflammatory disorders in other organs, such as the gastrointestinal tract and the lungs. Given these emerging roles, strategies to specifically target the expression and activity of the IL-36 family have the potential to uncover novel therapeutic approaches aimed at treating inflammatory diseases in humans.
MeSH term(s)	Gene Expression ; Humans ; Inflammation/genetics ; Inflammation/immunology ; Inflammation Mediators/immunology ; Inflammatory Bowel Diseases/genetics ; Inflammatory Bowel Diseases/immunology ; Interleukin-1/chemistry ; Interleukin-1/genetics ; Interleukin-1/immunology ; Interleukins/chemistry ; Interleukins/genetics ; Interleukins/immunology ; Models, Immunological ; Mutation ; Psoriasis/genetics ; Psoriasis/immunology
Chemical Substances	IL36A protein, human ; IL36B protein, human ; IL36G protein, human ; IL36RN protein, human ; Inflammation Mediators ; Interleukin-1 ; Interleukins
Language	English
Publishing date	2016-10-26
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	211003-9
ISSN	1749-6632 ; 0077-8923
ISSN (online)	1749-6632
ISSN	0077-8923
DOI	10.1111/nyas.13280
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