# Increased Colonic Levels of CD8+ Cytotoxic T lymphocyte-Associated Mediators in Patients With Microscopic Colitis

**Authors:** Alexandra Lushnikova, Anna Wickbom, Johan Bohr, Robert Kruse, Anders Wirén, Elisabeth Hultgren Hörnquist

PMC · DOI: 10.1093/ibd/izaf064 · Inflammatory Bowel Diseases · 2025-04-10

## TL;DR

Patients with microscopic colitis show higher levels of immune-related molecules linked to CD8+ T cells, suggesting a different disease mechanism compared to ulcerative colitis.

## Contribution

The study identifies distinct immune mediator profiles in microscopic colitis compared to ulcerative colitis and controls.

## Key findings

- Granzyme B and CCL5 levels were higher in active collagenous colitis than in ulcerative colitis.
- Microscopic colitis showed increased levels of CD8+ T cell-associated mediators compared to controls.
- MMP-1 and MMP-3 levels were higher in collagenous colitis than in lymphocytic colitis.

## Abstract

For unidentified reasons, possibly due to increased immune surveillance, patients with collagenous colitis (CC) and lymphocytic colitis (LC), both forms of microscopic colitis (MC), have lower risk of colorectal cancer than controls and ulcerative colitis (UC) patients. Levels of secreted and cell-bound mediators in MC patients with active disease and in histological remission (HR) compared to UC patients and controls were investigated.

Median fluorescence intensity of 54 analytes in colonic biopsies from patients with active CC (n = 21), LC (n = 11), and UC (n = 19); CC-HR (n = 6), LC-HR (n = 9), UC in remission (n = 19), non-diarrhea controls (n = 48), and diarrhea controls (n = 25) was measured using Luminex.

Granzyme B and CCL5 levels were higher in active CC than in UC, whereas CCL4 and CD163 levels were similar in CC and UC, and both groups had higher levels of matrix metalloproteinase (MMP)-1, MMP-3, and tumor necrosis factor receptor II than both control groups. APRIL, BAFF, BCMA, CCL20, CXCL8, chitinase 3-like 1, pentraxin-3, Fas, and IL-33 were higher in UC than MC. Increases in 4-1BB and perforin in MC compared to controls were lower than in UC. Levels of gp130 and IL-6Rα were decreased in MC but increased in UC compared to controls.

Microscopic colitis patients exhibit increased levels of several analytes, including some associated with CD8+ T lymphocytes, suggesting a different pathogenesis of MC compared to UC. Higher levels of MMP-1 and MMP-3 in CC than LC indicate separate disease entities.

Graphical Abstract

## Linked entities

- **Proteins:** CCL5 (C-C motif chemokine ligand 5), CCL4 (C-C motif chemokine ligand 4), CD163 (CD163 molecule), MMP1 (matrix metallopeptidase 1), MMP3 (matrix metallopeptidase 3), TNFSF13 (TNF superfamily member 13), TNFSF13B (TNF superfamily member 13b), TNFRSF17 (TNF receptor superfamily member 17), CCL20 (C-C motif chemokine ligand 20), CXCL8 (C-X-C motif chemokine ligand 8), FAS (Fas cell surface death receptor), IL33 (interleukin 33), TNFRSF9 (TNF receptor superfamily member 9), PRF1 (perforin 1), IL6ST (interleukin 6 cytokine family signal transducer), IL6R (interleukin 6 receptor)
- **Diseases:** collagenous colitis (MONDO:0000703), lymphocytic colitis (MONDO:0000704), microscopic colitis (MONDO:0000702), colorectal cancer (MONDO:0005575), ulcerative colitis (MONDO:0005101)

## Full-text entities

- **Genes:** CCL5 (C-C motif chemokine ligand 5) [NCBI Gene 6352] {aka D17S136E, RANTES, SCYA5, SIS-delta, SISd, TCP228}, GZMB (granzyme B) [NCBI Gene 3002] {aka C11, CCPI, CGL-1, CGL1, CSP-B, CSPB}, CXCL8 (C-X-C motif chemokine ligand 8) [NCBI Gene 3576] {aka GCP-1, GCP1, IL8, LECT, LUCT, LYNAP}, CD163 (CD163 molecule) [NCBI Gene 9332] {aka M130, MM130, SCARI1}, TNFRSF17 (TNF receptor superfamily member 17) [NCBI Gene 608] {aka BCM, BCMA, CD269, TNFRSF13A}, CHI3L1 (chitinase 3 like 1) [NCBI Gene 1116] {aka ASRT7, CGP-39, GP-39, GP39, HC-gp39, HCGP-3P}, TNFRSF9 (TNF receptor superfamily member 9) [NCBI Gene 3604] {aka 4-1BB, CD137, CDw137, ILA, IMD109}, FAS (Fas cell surface death receptor) [NCBI Gene 355] {aka ALPS1A, APO-1, APT1, CD95, FAS1, FASTM}, CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}, IL6ST (interleukin 6 cytokine family signal transducer) [NCBI Gene 3572] {aka CD130, CDW130, GP130, HIES4, HIES4A, HIES4B}, CCL20 (C-C motif chemokine ligand 20) [NCBI Gene 6364] {aka CKb4, Exodus, LARC, MIP-3-alpha, MIP-3a, MIP3A}, TNFSF13B (TNF superfamily member 13b) [NCBI Gene 10673] {aka BAFF, BLYS, CD257, TALL-1, TALL1, THANK}, CCL4 (C-C motif chemokine ligand 4) [NCBI Gene 6351] {aka ACT2, AT744.1, G-26, HC21, LAG-1, LAG1}, MMP3 (matrix metallopeptidase 3) [NCBI Gene 4314] {aka CHDS6, MMP-3, SL-1, STMY, STMY1, STR1}, IL6R (interleukin 6 receptor) [NCBI Gene 3570] {aka CD126, HIES5, IL-1Ra, IL-6R, IL-6R-1, IL-6RA}, MMP1 (matrix metallopeptidase 1) [NCBI Gene 4312] {aka CLG}, PTX3 (pentraxin 3) [NCBI Gene 5806] {aka TNFAIP5, TSG-14}, IL33 (interleukin 33) [NCBI Gene 90865] {aka C9orf26, DVS27, IL1F11, NF-HEV, NFEHEV}
- **Diseases:** CC (MESH:D046729), MC (MESH:D046728), UC (MESH:D003093), colorectal cancer (MESH:D015179), diarrhea (MESH:D003967), LC (MESH:D046730)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12342803/full.md

## References

40 references — full list in the complete paper: https://tomesphere.com/paper/PMC12342803/full.md

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Source: https://tomesphere.com/paper/PMC12342803