Ulcerative Colitis

JAK Pairings

Introduction

Signalling Through JAKs

JAK-containing protein complexes mediate essential functions such as haematopoiesis and pathogen immunity through normal cytokine signalling.^1,2

Excessive signalling through the JAK-STAT pathway results in atypical cytokine production and a cycle of chronic, relapsing inflammation, and potential damage in UC.^1,3

JAK Combinations

Downstream effects of JAK-STAT pathway activation: In health and disease

Selective JAK pairings that mediate cytokine signalling

IBD pathogenesis*

Inflammation⁴
Deleterious impact on wound healing⁵
Proinflammatory cytokine production in mucosa, tumour development⁶

Normal physiology*

Lymphocyte proliferation and homeostasis^14,15Adaptive immune response, intestinal homeostasis⁹
Humoral immunity, mucus production, anti-helminth defence¹⁵

Chronic intestinal epithelial inflammation^5,7
Proinflammatory cytokine production⁵
Increased permeability of intestinal epithelial barrier^5,8,9
Intestinal epithelial cell apoptosis and ulceration^8,10Epithelial cell proliferation and tumour growth (colorectal carcinogenesis)^7,10,11

T-cell differentiation and inflammation³
Wound healing⁵
Defence from extracellular pathogens¹⁵
Lipid metabolism¹⁶

Epithelial cell death⁷
Disruption and loss of epithelial barrier function¹⁰

Antiviral and antimicrobial immunity^15,16
Epithelial barrier protection^5,17Homeostasis of mucosal surfaces¹⁷

Not applicable

Erythropoiesis, myelopoiesis, and platelet production¹⁸
Growth¹⁶
Intestinal epithelium protection⁵

IBD susceptibility¹²
Proinflammatory cytokine production¹³

Antiviral, antitumour defences^15,16
Epithelial regeneration and maintenance of intestinal barrier^5,9

* The physiological processes listed here are examples of the unique JAK roles and do not provide an exhaustive list.

JAK-STAT Pathway

Find out more about the JAK-STAT pathway in UC.

JAK-STAT Function

Find out why the JAK-STAT pathway is of particular therapeutic interest in UC.

IBD, inflammatory bowel disease; JAK, Janus kinase; STAT, signal transducer and activator of transcription; UC, ulcerative colitis.

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