Foxp3 Expression Patterns in Microscopic Colitides

Abstract

Microscopic colitides, including lymphocytic (LC) and collagenous colitis (CC), are well-described pathologic conditions. An altered immune response is implicated in the pathogenesis of both entities. CD8+ T lymphocytes (CTLs) secrete interleukin 2 which stimulates proliferation of regulatory T cells (Tregs), and Tregs, in turn, inhibit CTLs, inducing cytotoxic tissue damage. In Tregs, Foxp3 regulates T-cell-related immune responses. The distribution of Tregs and CTLs in microscopic colitides has remained underexplored. To characterize differences in the distribution pattern of Foxp3 in biopsy specimens from patients with LC and CC, 71 colonic biopsy specimens from 69 consecutive patients were categorized into 1 of 3 diagnoses: no significant histopathologic abnormality (NSHPA), LC, or CC. Further immunohistochemical evaluation of all biopsy specimens was conducted using a panel of markers including CD8 and Foxp3. Our study demonstrated that CTL distribution pattern differences exist among these 2 colitides and that differences in the immunologic recruitment of Foxp3+ Tregs in the colonic mucosa correlate with differences in the spectrum of morphologic changes seen in patients with either LC or CC.

Systematic review with meta‐analysis: diagnostic overlap of microscopic colitis and functional bowel disorders

“…While there are several specific histological differences that distinguish lymphocytic colitis from collagenous colitis, both entities have a considerable clinical and therapeutic overlap . It is still unclear whether collagenous colitis and lymphocytic colitis should be considered two distinct entities or different subtypes of the same disease, since recent research has identified differences in the pathological mechanisms underlying the development and maintenance of the two subtypes, albeit in a common pathogenetic context …”

Histology of microscopic colitis—review with a practical approach for pathologists

“…in nine of 65 (14%) patients: three from collagenous to lymphocytic colitis, and six from lymphocytic to collagenous colitis. In another report, two patients were diagnosed with lymphocytic colitis at the beginning of the study, but were found to have collagenous colitis on later follow‐up biopsies . These data, however, need to be confirmed in further studies, as the overlap of histological features together with the patchy, non‐uniform distribution of both diseases along the colon might lead to an erroneous assumption of true conversion if the number of sampled biopsies is small.…”

“…The notion of a histological overlap between lymphocytic and collagenous colitis and the rare occurrence of disease conversion caused some authors to conclude that lymphocytic and collagenous colitis are in fact two histological manifestations of the same disease entity, possibly representing different manifestations during the disease course or different stages of disease development . This hypothesis is, however, still lacking further evidence, in particular experimental evidence, and a definitive conclusion cannot be drawn.…”

The Role of T-Cell Subsets in Chronic Inflammation in Celiac Disease and Inflammatory Bowel Disease Patients: More Common Mechanisms or More Differences?

“…About 60% of the CD4 + LPL were GATA-3 + [144] pointing to Th2 cells activated by TCR dependent or independent of the IL-4 receptor [146]. Treg counts are more increased in collagenous than in lymphocytic colitis [147]. In patients initially diagnosed with lymphocytic colitis that later developed collagenous colitis, overall IEL numbers dropped while Treg counts increased [147].…”

“…Treg counts are more increased in collagenous than in lymphocytic colitis [147]. In patients initially diagnosed with lymphocytic colitis that later developed collagenous colitis, overall IEL numbers dropped while Treg counts increased [147]. …”