Jason E. Hawkes, MD, Tom C. Chan, MD, PhD, James G. Krueger, MD, PhD

Slides:

Advertisements

Similar presentations

“Inflammatory skin march”: IL-1–mediated skin inflammation, atopic dermatitis, and psoriasis to cardiovascular events Keiichi Yamanaka, MD, PhD, Hitoshi.

Advertisements

Clarification concerning amoxicillin skin testing

Roles of Mas-related G protein–coupled receptor X2 on mast cell–mediated host defense, pseudoallergic drug reactions, and chronic inflammatory diseases

Low-dose methotrexate-induced ulcerated psoriatic plaques: A rare case

MicroRNA-146a suppresses IL-17–mediated skin inflammation and is genetically associated with psoriasis Ankit Srivastava, MTech, Pernilla Nikamo, PhD,

Natalija Novak, MD Journal of Allergy and Clinical Immunology

Fatty acids, inflammation, and asthma

Laurent L'homme, PhD, David Dombrowicz, PhD

Advances in food allergy in 2015

Links between the innate immune system and sleep

Santa Jeremy Ono, BA, PhD, Mark B. Abelson, MD

The role of viruses in acute exacerbations of asthma

Atopic dermatitis: Age and race do matter!

Prostaglandin E2 suppresses CCL27 production through EP2 and EP3 receptors in human keratinocytes Naoko Kanda, MD, PhD, Hiroshi Mitsui, MD, PhD, Shinichi.

Atopic dermatitis results in intrinsic barrier and immune abnormalities: Implications for contact dermatitis Julia K. Gittler, BA, James G. Krueger,

Inflammatory marker analysis in psoriatic skin under topical phosphodiesterase 4 inhibitor treatment Lennart M. Roesner, PhD, Petra Kienlin, Gabriele.

Progressive activation of TH2/TH22 cytokines and selective epidermal proteins characterizes acute and chronic atopic dermatitis Julia K. Gittler, BA,

Jason E. Hawkes, MD, Tom C. Chan, MD, PhD, James G. Krueger, MD, PhD

Therapeutic pipeline for atopic dermatitis: End of the drought?

Is 9 more than 2 also in allergic airway inflammation?

Thomas F. Tedder, PhD, Takashi Matsushita, MD, PhD

Interplay between the skin barrier and immune cells in patients with atopic dermatitis unraveled by means of mathematical modeling David Bending, PhD,

IL-17A is essential for cell activation and inflammatory gene circuits in subjects with psoriasis James G. Krueger, MD, Scott Fretzin, MD, Mayte Suárez-Fariñas,

Shinji Noda, MD, PhD, James G

Fatty acids, inflammation, and asthma

TNF-α–induced protein 3 (A20): The immunological rheostat

The Multitasking Organ: Recent Insights into Skin Immune Function

IL-22–producing “T22” T cells account for upregulated IL-22 in atopic dermatitis despite reduced IL-17–producing TH17 T cells Kristine E. Nograles, MD,

Identification of TNF-related apoptosis-inducing ligand and other molecules that distinguish inflammatory from resident dendritic cells in patients with.

Yuichi Teraki, MD, Aika Sakurai, MD, Seiichi Izaki, MD

Antimicrobial peptides and the skin immune defense system

The Multitasking Organ: Recent Insights into Skin Immune Function

Immune modulation by neuronal electric shock waves

TH17 and TH22 cells: A confusion of antimicrobial response with tissue inflammation versus protection Mübeccel Akdis, MD, PhD, Oscar Palomares, PhD,

Inflammatory health effects of indoor and outdoor particulate matter

Innate lymphoid cells in allergic and nonallergic inflammation

Epithelium: At the interface of innate and adaptive immune responses

Antiviral activity of human β-defensin 3 against vaccinia virus

Role of IgE in autoimmunity

Time for a paradigm shift in asthma treatment: From relieving bronchospasm to controlling systemic inflammation Leif Bjermer, MD Journal of Allergy.

Receptor-interacting protein kinase 3 controls keratinocyte activation in a necroptosis- independent manner and promotes psoriatic dermatitis in mice

Food allergy: A review and update on epidemiology, pathogenesis, diagnosis, prevention, and management Scott H. Sicherer, MD, Hugh A. Sampson, MD Journal.

Ryan P. Hobbs, Susan H. Smith, Spiro Getsios

Update on the role of prostaglandins in allergic lung inflammation: Separating friends from foes, harder than you might think Martin L. Moore, PhD, R.

Weiguo Chen, PhD, Gurjit K. Khurana Hershey, MD, PhD

Liam O’Mahony, PhD, Mübeccel Akdis, MD, PhD, Cezmi A. Akdis, MD

The eosinophil—quo vadis?

Autophagy: Nobel Prize 2016 and allergy and asthma research

IL-2– and CD25-dependent immunoregulatory mechanisms in the homeostasis of T-cell subsets Sven Létourneau, DPhil, Carsten Krieg, PhD, Giuseppe Pantaleo,

Food allergy: Epidemiology, pathogenesis, diagnosis, and treatment

The skin as an immune organ: Tolerance versus effector responses and applications to food allergy and hypersensitivity reactions Emma Guttman-Yassky,

New pathways for itching in patients with atopic dermatitis?

MicroRNA-146a suppresses IL-17–mediated skin inflammation and is genetically associated with psoriasis Ankit Srivastava, MTech, Pernilla Nikamo, PhD,

Chemokines and their receptors in allergic disease

Cytokines and chemokines orchestrate atopic skin inflammation

Cagri Yildirim-Toruner, MD, Betty Diamond, MD

One step forward, 2 steps back: The enigma of preschool wheeze

Does “autoreactivity” play a role in atopic dermatitis?

Expression of chemokines and chemokine receptors in lesional and nonlesional upper skin of patients with atopic dermatitis Eva Gros, MSc, Caroline Bussmann,

Thymic stromal lymphopoietin and OX40 ligand pathway in the initiation of dendritic cell–mediated allergic inflammation Yong-Jun Liu, MD, PhD Journal.

Innate immune responses to infection

Innate lymphoid cells in allergic and nonallergic inflammation

Natural killer cell biology: An update and future directions

Asthma: The past, future, environment, and costs

Genetic regulation of IgE responses: Achilles and the tortoise

Contrasting pathogenesis of atopic dermatitis and psoriasis—Part II: Immune cell subsets and therapeutic concepts Emma Guttman-Yassky, MD, PhD, Kristine.

Cytokines: IL-20 — a new effector in skin inflammation

Natural history of cow’s milk allergy

Primary prevention of asthma and allergy

Chitinases and chitinase-like proteins in TH2 inflammation and asthma

Presentation transcript:

Psoriasis pathogenesis and the development of novel targeted immune therapies Jason E. Hawkes, MD, Tom C. Chan, MD, PhD, James G. Krueger, MD, PhD Journal of Allergy and Clinical Immunology Volume 140, Issue 3, Pages 645-653 (September 2017) DOI: 10.1016/j.jaci.2017.07.004 Copyright © 2017 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 IL-23/T17–mediated effects on epidermal keratinocytes (KCs) in psoriatic skin. Schematic showing the broad downstream effects of increased IL-23 and IL-17 signaling on various immune cell populations and keratinocyte biology. Regulated by IL-23, the primary effects of IL-17 on keratinocytes include indirect induction of epidermal hyperplasia through IL-19 and IL-36, upregulation of the innate immune response and AMPs (eg, hBD2, S100A7, and LL-37), epidermal recruitment of leukocyte subsets (eg, neutrophils and mDCs) through increased production of keratinocyte-derived chemokines, and transcription of multiple proinflammatory genes (eg, IL-1β, IL-6, and IL-8) that act synergistically with TNF to sustain the inflammatory events in psoriatic skin. Journal of Allergy and Clinical Immunology 2017 140, 645-653DOI: (10.1016/j.jaci.2017.07.004) Copyright © 2017 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 IL-17–driven initiation of feed forward inflammation in keratinocytes and induction of psoriatic plaques. A working model of psoriasis showing activation and upregulation of IL-17 in a type 17 resident memory T cell (Trm) in prepsoriatic skin. Increased production of IL-17 results in activation of the IL-17 receptor (IL17R) on viable keratinocytes and a feed forward inflammatory response through activation of IL-17–induced transcription factors (eg, C/EBPβ). This feed forward inflammatory response in keratinocytes is self-amplifying and promotes the development of mature psoriatic plaques through recruitment of pathogenic immune cells, epidermal hyperplasia, and overproduction of IL-17–induced keratinocyte-derived gene products (eg, S100A7/8/9, hBD2, lipocalin-2 [LCN2], and CCL20), which are noticeably increased in the upper layers of the epidermis. A granular layer can be absent in mature psoriasis lesions, leading to retained nuclei in surface corneocytes (ie, parakeratosis). Tem, Effector memory T cell. Journal of Allergy and Clinical Immunology 2017 140, 645-653DOI: (10.1016/j.jaci.2017.07.004) Copyright © 2017 American Academy of Allergy, Asthma & Immunology Terms and Conditions