The complexity of asthma is underscored by the number of cell types and mediators implicated in the pathogenesis of this heterogeneous syndrome. Type 2 CD4⁺T-cells (Th2) and more recently, type 2 innate lymphoid cells dominate current descriptions of asthma pathogenesis. However, another important source of these type 2 cytokines, especially interleukin (IL)-5 and IL-13, are CD8⁺T-cells, which are increasingly proposed to play an important role in asthma pathogenesis, because they are abundant and are comparatively insensitive to corticosteroids. Many common triggers of asthma exacerbations are mediatedviacorticosteroid-resistant pathways involving neutrophils and CD8⁺T-cells. Extensive murine data reveal the plasticity of CD8⁺T-cells and their capacity to enhance airway inflammation and airway dysfunction. In humans, Tc2 cells are predominant in fatal asthma, while in stable state, severe eosinophilic asthma is associated with greater numbers of Tc2 than Th2 cells in blood, bronchoalveolar lavage fluid and bronchial biopsies. Tc2 cells strongly express CRTH2, the receptor for prostaglandin D2, the cysteinyl leukotriene receptor 1 and the leukotriene B4 receptor. When activated, these elicit Tc2 cell chemotaxis and production of chemokines and type 2 and other cytokines, resulting directly or indirectly in eosinophil recruitment and survival. These factors position CD8⁺Tc2 cells as important and underappreciated effector cells contributing to asthma pathogenesis. Here, we review recent advances and new insights in understanding the pro-asthmatic functions of CD8⁺T-cells in eosinophilic asthma, especially corticosteroid-resistant asthma, and the molecular mechanisms underlying their pathologic effector function.

Mucosal-associated invariant T (MAIT) cells represent an innate T-cell population that can recognize ligands generated by the microbial riboflavin synthesis pathway, presented via the major histocompatibility complex class I–related molecule (MR1). Streptococcus pneumoniae is a major human pathogen that is also associated with commensal carriage; thus, host control at the mucosal interface is critical. The recognition of pneumococci by MAIT cells has not been defined nor have the genomics and transcriptomics of the riboflavin operon. We observed robust recognition of pneumococci by MAIT cells, using both MR1-dependent and MR1-independent pathways. The pathway used was dependent on the antigen-presenting cell. The riboflavin operon was highly conserved across a range of 571 pneumococci from 39 countries, dating back to 1916, and different versions of the riboflavin operon were also identified in related Streptococcus species. These data indicate an important functional relationship between MAIT cells and pneumococci.

Human type 2 cytotoxic T (Tc2) cells are enriched in severe eosinophilic asthma and can contribute to airway eosinophilia. PGD₂ and its receptor PGD₂ receptor 2 (DP2) play important roles in Tc2 cell activation, including migration, cytokine production, and survival. In this study, we revealed novel, to our knowledge, functions of the PGD₂/DP2 axis in Tc2 cells to induce tissue-remodeling effects and IgE-independent PGD₂ autocrine production. PGD₂ upregulated the expression of tissue-remodeling genes in Tc2 cells that enhanced the fibroblast proliferation and protein production required for tissue repair and myofibroblast differentiation. PGD₂ stimulated Tc2 cells to produce PGD₂ using the routine PGD₂ synthesis pathway, which also contributed to TCR-dependent PGD₂ production in Tc2 cells. Using fevipiprant, a specific DP2 antagonist, we demonstrated that competitive inhibition of DP2 not only completely blocked the cell migration, adhesion, proinflammatory cytokine production, and survival of Tc2 cells triggered by PGD₂ but also attenuated the tissue-remodeling effects and autocrine/paracrine PGD₂ production in Tc2 induced by PGD₂ and other stimulators. These findings further confirmed the anti-inflammatory effect of fevipiprant and provided a better understanding of the role of Tc2 cells in the pathogenesis of asthma. Key Points Multiple proinflammatory effects of Tc2 cells are inhibited by DP2 antagonism. Tissue-remodeling functions of Tc2 cells are attenuated by DP2 antagonism. Autocrine/paracrine PGD₂ production in Tc2 cells is reduced by DP2 antagonism.

Background and Aim: Standardisation is crucial for outcomes in minimally invasive colorectal surgery. Debate continues regarding the comparative efficacy of robotic versus laparoscopic platforms. This study evaluates perioperative outcomes for both approaches, performed by a single surgeon using an identical standardised technique to isolate the platform's effect. Methods: A retrospective cohort study of 250 patients undergoing colorectal resection (2019-2023) was conducted. Patients were divided into laparoscopic (n=121) and robotic (n=129) groups. Data included demographics, ASA grade, conversion rates, operative times, Clavien-Dindo complications, resection margin status (R0/R1), mortality, and length of stay. R software was used for analysis. Results: Demographics were matched, but fewer high-risk (ASA III) patients were in the robotic cohort (38.7% vs. 51.3%; p<0.05). The robotic approach showed a significantly lower conversion rate (0% vs. 6.6%). A non-significant trend toward higher-grade complications existed in the laparoscopic group (median grade II vs. I; p=0.12), with a significantly higher R1 resection rate (n=8 vs. n=2). Laparoscopic 30-day (2 vs. 0) and 90-day (4 vs. 0) mortality was higher. Anastomotic leak rates (1.6% each) and median hospital stay (5 days; p=0.71) were similar in both groups. Conclusion: Using a standardised technique, outcomes are comparable except for a significantly reduced conversion rate with robotics. The observed difference in R1 resection rates may be influenced by baseline differences in patient populations. For skilled surgeons, the choice of platform may be influenced more by economic factors and preference than by major differences in clinical efficacy. What does this paper add to the literature? Debate continues regarding the comparative efficacy of robotic versus laparoscopic platforms. This single-surgeon study compares outcomes in colorectal cancer using minimally invasive procedures and a standardised technique. The result of similar clinical efficacy suggests that standardisation reduces outcome variability and demonstrates that cost and preference may influence platform choices more.