Changes in diet and microbiota have determining effects on the function of the mucosal immune system. For example, the active metabolite of vitamin A, retinoic acid (RA), has been described to maintain homeostasis in the intestine by its influence on both lymphocytes and myeloid cells. Additionally, innate lymphoid cells (ILCs), important producers of cytokines necessary for intestinal homeostasis, are also influenced by vitamin A in the small intestines. In this study, we show a reduction of both NCR⁻ and NCR⁺ ILC3 subsets in the small intestine of mice raised on a vitamin A–deficient diet. Additionally, the percentages of IL-22–producing ILCs were reduced in the absence of dietary vitamin A. Conversely, mice receiving additional RA had a specific increase in the NCR⁻ ILC3 subset, which contains the lymphoid tissue inducer cells. The dependence of lymphoid tissue inducer cells on vitamin A was furthermore illustrated by impaired development of enteric lymphoid tissues in vitamin A–deficient mice. These effects were a direct consequence of ILC-intrinsic RA signaling, because retinoic acid–related orphan receptor γt–Cre × RARα-DN mice had reduced numbers of NCR⁻ and NCR⁺ ILC3 subsets within the small intestine. However, lymphoid tissue inducer cells were not affected in these mice nor was the formation of enteric lymphoid tissue, demonstrating that the onset of RA signaling might take place before retinoic acid–related orphan receptor γt is expressed on lymphoid tissue inducer cells. Taken together, our data show an important role for vitamin A in controlling innate lymphoid cells and, consequently, postnatal formed lymphoid tissues within the small intestines.

Despite improvements in cancer therapy, metastatic solid tumors remain largely incurable. Immunotherapy has emerged as a pioneering and promising approach for cancer therapy and management, and in particular intended for advanced tumors unresponsive to current therapeutics. In cancer immunotherapy, components of the immune system are exploited to eliminate cancer cells and treat patients. The recent clinical successes of immune checkpoint blockade and chimeric antigen receptor T cell therapies represent a turning point in cancer treatment. Despite their potential success, current approaches depend on efficient tumor antigen presentation which are often inaccessible, and most tumors turn refractory to current immunotherapy. Patient-derived induced pluripotent stem cells (iPSCs) have been shown to share several characteristics with cancer (stem) cells (CSCs), eliciting a specific anti-tumoral response when injected in rodent cancer models. Indeed, artificial cellular reprogramming has been widely compared to the biogenesis of CSCs. Here, we will discuss the state-of-the-art on the potential implication of cellular reprogramming and iPSCs for the design of patient-specific immunotherapeutic strategies, debating the similarities between iPSCs and cancer cells and introducing potential strategies that could enhance the efficiency and therapeutic potential of iPSCs-based cancer vaccines.

The origin of gastrointestinal symptoms compatible with irritable bowel syndrome (IBS) in patients with inflammatory bowel disease in remission is a challenge. Our aim was to prospectively determine the relation of IBS symptoms with calprotectin levels (FC), endoscopic Mayo score and histologic findings, in patients with ulcerative colitis (UC) in clinical remission. Patient recruitment was between January – March of 2020 and November of 2020 - August of 2021 and included consecutive UC patients in clinical remission and scheduled for a colonoscopy. Clinical remission was defined by a stool frequency ≤3/day with no bleeding, ulcerative colitis activity index <4 and serum C-reactive protein lower than 1mg/dL. Exclusion criteria were therapeutic with corticosteroids over the prior 6 months or initiation of biological agents in the last 6 months. IBS diagnosis was evaluated by Roma IV criteria (IBS-like group). FC level was assessed before colonoscopy and during the exam Mayo endoscopy subscore was applied and random biopsies of all segments of colon and rectum were made to achieve histologic activity using Geboes index. This study was approved by Centro Hospitalar e Universitário de Coimbra Ethics Committee. A total of 106 patients (50% women; mean age 51 years ±14.8) were included. The mean of disease duration was 15.7 years (±9.06) and 13 of them (12.3%) had proctitis, 64 (60%) left-sided colitis and 29 (27.4%) extensive colitis. Regarding disease activity: mean FC was 189.48mg/Kg (±382), endoscopic Mayo score lower than 1 was found in 63 patients (59.4%) and Geboes index lower than 1.1 was found in 66 patients (62.3%). Rome IV criteria for IBS were fulfilled by 29 patients (27.4%). The IBS-like group showed FC levels significantly higher (303±483mg/Kg vs. 139±319mg/Kg; P1.1 in 65,5% vs. 27.3%, P0.05). IBS-like symptoms are common in patients with UC considered to be in clinical remission. Higher levels of FC and histological activity support the idea of the presence of subclinical inflammation rather than coexistent IBS.