Distinct Alterations in the Composition of Mucosal Innate Lymphoid Cells in Newly Diagnosed and Established Crohn’s Disease and Ulcerative Colitis

Forkel, Marianne; Tol, Sophie van; Höög, Charlotte; Michaëlsson, Jakob; Almér, Sven; Mjösberg, Jenny

doi:10.1093/ecco-jcc/jjy119

Cited by 104 publications

(177 citation statements)

References 45 publications

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“…The major cytokine produced by ILC3s is IL22, and a population of ILC3s also produces IL-17 [7]. The view of cytokine profile indicates that ILCs are involved in the pathophysiology of IBD [8]. In patients with CD, IFN-c-producing ILC1s and IL-17-producing ILC3s accumulate in the inflamed tissue with a decreased number of IL-22 producing ILC3s.…”

Section: The Pathophysiology and Treatment Of Ibd From The Perspectivmentioning

confidence: 99%

Treatment of inflammatory bowel disease from the immunological perspective

Nakase

2020

Immunological Medicine

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Since 1950, the number of patients with inflammatory bowel disease (IBD) in Japan has been increasing. Recent research data indicate that the pathophysiology of IBD involves abnormalities in disease susceptibility genes, environmental factors and intestinal bacteria. The elucidation of the mechanism of IBD has facilitated therapeutic development based on basic research data. In particular, the emergence of biologics has brought about a paradigm shift in the treatment of IBD. However, there are still IBD patients who are refractory to these biologics. IBD pathophysiology is extremely complex. Therefore, to address these clinical issues, further clinical and basic data are required. The bottom line of IBD drug therapy is still to use the most of recent treatments. Therefore, the physicians should be familiar with the modes of action (MOA) of the available drugs.

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Section: The Pathophysiology and Treatment Of Ibd From The Perspectivmentioning

confidence: 99%

Treatment of inflammatory bowel disease from the immunological perspective

Nakase

2020

Immunological Medicine

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“…Supporting the role of Group 1 ILCs in driving disease-associated gut pathology, frequencies of NK cells or ILC1s were increased in Crohn's disease or Ulcerative colitis (types of IBD) and in some studies, IFNγ-producing Group 1 ILCs were increased. [16][17][18][19] In the context of HIV, we have reported an increase in IFNγproducing NKp44+ CD56+ ILCs (a population of cells likely to include both NK cells and ILC1s) in the colonic mucosa of people living with HIV (PLWH) who are naïve to treatment. 20 Increases in IFNγ-producing and cytotoxic colonic ILCs (defined as CD3-NKp44+) were also reported in Rhesus macaques infected with SIV (the nonhuman primate model of HIV).…”

Section: Introductionmentioning

confidence: 99%

Enteric bacteria induce IFNγ and Granzyme B from human colonic Group 1 Innate Lymphoid Cells

et al. 2019

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Group 1 Innate Lymphoid Cells (which include Natural Killer cells and ILC1s) aid in gut antibacterial defense through the production of IFNγ, which is critical for mobilizing protective responses against enteric pathogens. When intestinal epithelial barrier integrity is compromised, commensal bacteria are likely to translocate from the gut lumen into the lamina propria. Few studies have addressed the mechanisms by which commensal bacteria impact the function of gut Group 1 ILCs, especially ILC1s. Utilizing an in vitro human colonic lamina propria mononuclear cell (LPMC) model, we evaluated Group 1 ILC cytokine and cytolytic protein production in response to a panel of enteric Gram-positive and Gram-negative commensal and pathogenic bacteria. IFNγproduction by NK cells and ILC1s was significantly increased after LPMC exposure to Gramnegative commensal or pathogenic bacteria, but not after exposure to the Gram-positive bacteria commensals tested. Stimulation of IFNγ production from Group 1 ILCs was not through direct recognition of bacteria by NK cells or ILC1s, but rather required accessory cells within the LPMC population. Myeloid dendritic cells generated IL-12p70, IL-18, and IL-1β upon exposure to enteric bacteria and these cytokines contributed to Group 1 ILC production of IFNγ. Furthermore, Gramnegative commensal or pathogenic bacteria induced significant expression of Granzyme B in NK cells and ILC1s. Overall, these data demonstrate that some enteric commensal bacteria indirectly induce inflammatory cytokine production and cytolytic protein expression from human colonic Group 1 ILCs, a process which could contribute to inflammation in the setting of microbial translocation.

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“…In fact, they are found to a relative lower frequency compared to other ILC subsets that reside in the intestine. Nevertheless, ILC2 frequency is increased in mucosal samples from IBD patients compared with healthy individuals (74). In CRC tumors, ILC2s express higher levels of ICOS and CD69 compared with ILC2 found in normal colon tissue (59,60).…”

Section: Type 2 Innate Lymphoid Cellsmentioning

confidence: 95%

Innate Lymphoid Cells in Colorectal Cancers: A Double-Edged Sword

et al. 2020

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The immune system plays a fundamental role at mucosal barriers in maintaining tissue homeostasis. This is particularly true for the gut where cells are flooded with microbial-derived signals and antigens, which constantly challenge the integrity of the intestinal barrier. Multiple immune cell populations equipped with both pro-and anti-inflammatory functions reside in the gut tissue and these cells tightly regulate intestinal health and functions. Dysregulation of this finely tuned system can progressively lead to autoimmune disease and inflammation-driven carcinogenesis. Over the last decade, the contribution of the adaptive immune system in controlling colorectal cancer has been studied in detail, but the role of the innate system, particularly innate lymphoid cells (ILCs), have been largely overlooked. By sensing their microenvironment, ILCs are essential in supporting gut epithelium repair and controling bacterial-and helminth-mediated intestinal infections, highlighting their important role in maintaining tissue integrity. Accumulating evidence also suggests that they may play an important role in carcinogenesis including intestinal cancers. In this review, we will explore the current knowledge about the pro-and anti-tumor functions of ILCs in colorectal cancer.

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Distinct Alterations in the Composition of Mucosal Innate Lymphoid Cells in Newly Diagnosed and Established Crohn’s Disease and Ulcerative Colitis

Cited by 104 publications

References 45 publications

Treatment of inflammatory bowel disease from the immunological perspective

Treatment of inflammatory bowel disease from the immunological perspective

Enteric bacteria induce IFNγ and Granzyme B from human colonic Group 1 Innate Lymphoid Cells

Innate Lymphoid Cells in Colorectal Cancers: A Double-Edged Sword

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