Deficiency of Invariant NK T Cells in Crohn's Disease and Ulcerative Colitis

Abstract Background and Aims CD14+ mononuclear phagocytes [MNPs] and T cells infiltrate colon in ulcerative colitis [UC]. Here we investigated how CD14+ MNPs and the cytokines they produce shape the colonic effector T cell profile. Methods Colonic or mesenteric lymph node [mLNs] CD4+ T cells isolated from UC or Crohn’s disease [CD] patients were stimulated with cytokines or autologous CD14+ MNPs. Cytokine expression was assessed by intracytoplasmic staining and multiplex ELISA. Unsupervised phenotypic multicolour analysis of colonic CD14+ MNPs was performed using the FlowSOM algorithm. Results Among CD14+CD64+HLA-DR+SIRPα + MNPs, only the pro-inflammatory cytokine-producing CD163− subpopulation accumulated in inflamed UC colon and promoted mucosal IL-1β-dependent Th17, Th17/Th1, Th17/Th22 but not Th1 responses. Unsupervised phenotypic analysis of CD14+CD64+ MNPs segregated CD163− monocyte-like cells and CD163+ macrophages. Unexpectedly, IL-12, IL-1β and CD163−, but not CD163+, cells induced IL-8 expression in colonic CD4+ T cells, which co-expressed IFN-γ and/or IL-17 in UC and not CD. The CD163− monocyte-like cells increased the frequency of IL-8+IL-17+/−IFN-γ +/− T cells through IL-1β and IL-12. Finally, colonic IL-8+ T cells co-expressing GM-CSF, TNF-α and IL-6 were detected ex vivo and, promoted by IL-12 in the mucosa and mLNs in UC only. Conclusions Our findings established a link between monocyte-like CD163− MNPs, IL-12, IL-1β and the detection of colonic memory IL-8-producing CD4+ T cells, which might all contribute to the pathogenesis of UC.

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85 DIFFERENTIAL GROWTH AND CLONALITY OF GUT T-CELLS AMONG CROHN'S DISEASE (CD), ULCERATIVE COLITIS (UC), UNDETERMINED INFLAMMATION (NON-IBD) AND CONTROL CHILDREN

Journal of Pediatric Gastroenterology and Nutrition ◽

10.1097/00005176-199610000-00115 ◽

1996 ◽

Vol 23 (3) ◽

pp. 363

Author(s):

S Kugathasan ◽

D G Binion ◽

J T Boyle ◽

C Fiocchi

Keyword(s):

Ulcerative Colitis ◽

T Cells ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Differential Growth ◽

And Control

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Divergent cell cycle kinetics underlie the distinct functional capacity of mucosal T cells in Crohn's disease and ulcerative colitis

Gut ◽

10.1136/gut.2003.033613 ◽

2004 ◽

Vol 53 (11) ◽

pp. 1624-1631 ◽

Cited By ~ 55

Author(s):

A Sturm

Keyword(s):

Cell Cycle ◽

Ulcerative Colitis ◽

T Cells ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Functional Capacity ◽

Cell Cycle Kinetics ◽

Mucosal T Cells

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P007 Identification and characterisation of intestine-derived circulating resident memory T cells (ex-Trm) in health and Inflammatory Bowel Disease

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjab076.136 ◽

2021 ◽

Vol 15 (Supplement_1) ◽

pp. S128-S128

Author(s):

B Rodger ◽

I Hoti ◽

H Gordon ◽

J Lindsay ◽

A Stagg

Keyword(s):

Ulcerative Colitis ◽

T Cells ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Mononuclear Cells ◽

Intestinal Inflammation ◽

Memory T Cells ◽

Peripheral Blood Mononuclear ◽

Peripheral Tissues ◽

Resident Memory T Cells

Abstract Background Tissue resident memory T cells (Trm) persist in peripheral tissues where they protect against pathogens but can also contribute to inflammatory disease. Recent work shows that Trm can re-enter the circulation and give rise to new effector T cell and Trm populations in secondary tissue sites. Such ‘ex -Trm’ derived from the skin co-express the residency marker CD103 with cutaneous leukocyte antigen (CLA), a marker associated with skin tropism. Many T cells in the human intestine are Trm but it is unknown whether these cells re-enter the circulation; the existence of gut-derived ex-Trm would have important implications for IBD treatment targeting the recruitment of circulating gut-homing cells. Here, we identify a population of blood cells that co-express CD103 and the gut-homing integrin a4b7 and determine how they are changed in IBD. Methods Peripheral blood mononuclear cells (PBMCs) were isolated from healthy volunteers and patients with active IBD (Crohn’s disease or ulcerative colitis). Cell surface staining and multi-colour flow cytometry were used to identify CD4+ and CD8+ subsets of antigen experienced (CD45RA-) conventional T cells (abTCR+) and determine expression of markers associated with tissue tropism and residency. Results Staining with antibodies to CD103 and b7 integrin were used to define CD103b7+a4b7+ putative gut ex-Trm based on the excess per cell expression of b7 resulting from its contribution to both integrins. A separate CD103b7+a4b7- population defined by 1:1 expression of CD103 and b7 contained CLA+ skin ex-Trm. Gut ex-Trm comprised 0.3% total circulating CD8+ T cells (range 0.02–1.4%), and 1.2% CD4+ T cells (range 0.3–3%). Gut and skin ex-Trm were phenotypically similar; both expressed the residency associated markers CD101 and CD9 but lacked expression of CD69. Gut ex-Trm were phenotypically distinct from both traditional CD103-a4b7+ gut tropic CD45RA- antigen-experienced T cells and naïve T cells; significantly more gut ex-Trm expressed CD101 and CD9 and fewer expressed CD27. The proportion of gut ex-Trm did not differ between heath and IBD. However, the ratio of gut:skin ex Trm was significantly reduced in active Crohn’s disease but not ulcerative colitis indicating a selective reduction in the population derived from the intestine. Conclusion A putative population of gut-derived ex-Trm can be identified in the blood of healthy controls and IBD patients. This population has a distinctive phenotype similar to that of previously described skin-derived ex-Trm. Circulating ex-Trm could link discreet areas of intestinal inflammation in Crohn’s disease and there is a selective loss of the gut ex-Trm population from the blood of these patients. The role of ex-Trm in IBD merits further study.

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