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 homeostasis14,15
Adaptive immune response, intestinal homeostasis9
Humoral immunity, mucus production, anti-helminth defence15


Chronic intestinal epithelial inflammation5,7
Proinflammatory cytokine production5
Increased permeability of intestinal epithelial barrier5,8,9
Intestinal epithelial cell apoptosis and ulceration8,10
Epithelial 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 immunity15,16
Epithelial barrier protection5,17
Homeostasis of mucosal surfaces17


Not applicable


Erythropoiesis, myelopoiesis, and platelet production18
Growth16
Intestinal epithelium protection5


IBD susceptibility12
Proinflammatory cytokine production13


Antiviral, antitumour defences15,16
Epithelial regeneration and maintenance of intestinal barrier5,9

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

Related

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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