Immunological Reviews最新文献

Childhood is a multifactorial disease, and recent research highlights the influence of early-life microbial communities in shaping disease risk. This review explores the roles of the gut and respiratory microbiota in asthma development, emphasizing the importance of early microbial exposure. The gut microbiota has been particularly well studied, with certain taxa like Faecalibacterium and Bifidobacterium linked to asthma protection, whereas short-chain fatty acids produced by gut microbes support immune tolerance through the gut–lung axis. In contrast, the respiratory microbiota, though low in biomass, shows consistent associations between early bacterial colonization by Streptococcus, Moraxella, and Haemophilus and increased asthma risk. The review also addresses the emerging roles of the skin microbiota and environmental fungi in asthma, though findings remain inconsistent. Timing is a critical factor, with early-life disruptions, such as antibiotic use, potentially leading to increased asthma risk. Despite significant advances, there are still unresolved questions about the long-term consequences of early microbial perturbations, particularly regarding whether microbial dysbiosis is a cause or consequence of asthma. This review integrates current findings, highlighting the need for deeper investigation into cross-organ interactions and early microbial exposures to understand childhood asthma pathophysiology.

Asthma is one of the most prevalent and extensively studied chronic respiratory conditions, yet the heterogeneity of asthma remains biologically puzzling. Established factors like exogenous exposures and treatment adherence contribute to variability in asthma risk and clinical outcomes. It is also clear that the endogenous factors of genetics and immune system response patterns play key roles in asthma. Despite significant existing knowledge in the above, divergent clinical trajectories and outcomes are still observed, even among individuals with similar risk profiles, biomarkers, and optimal medical management. This suggests uncaptured biological interactions that contribute to asthma's heterogeneity, for which the role of host microbiota has lately attracted much research attention. This review will highlight recent evidence in this area, focusing on bedside-to-bench investigations that have leveraged omic technologies to uncover microbiome links to asthma outcomes and immunobiology. Studies centered on the respiratory system and the use of multi-omics are noted in particular. These represent a new generation of reverse-translational investigations revealing potential functional crosstalk in host microbiomes that may drive phenotypic heterogeneity in chronic diseases like asthma. Multi-omic data offer a wide lens into ecosystem interactions within a host. This informs new hypotheses and experimental work to elucidate mechanistic pathways for unresolved asthma endotypes. Further incorporation of multi-omics into patient-centered investigations can yield new insights that hopefully lead to even more precise, microbiome-informed strategies to reduce asthma burden.

W. L. Kan, C. M. Weekley, T. L. Nero, et al. “The β Common Cytokine Receptor Family Reveals New Functional Paradigms From Structural Complexities,” Immunological Reviews 329 (2025): e13430, https://doi.org/10.1111/imr.13430.

In the article, there was an error in the funding grant in the Acknowledgment.

The second sentence reads:

Hercus and A.F. Lopez (APP1148221) and Leukemia & Lymphoma Society Chronic Myelomonocytic Leukemia Special Initiative to R. Majeti, D. Thomas, and A.F. Lopez (LLS 8042-24).

The sentence should read:

Hercus and A.F. Lopez (APP1148221) and the Leukemia & Lymphoma Society with support from the Mike & Sofia Segal Foundation to R. Majeti, D. Thomas, and A.F. Lopez (LLS 8042-24).

We apologize for this error.

It has long been appreciated that farm exposure early in life protects individuals from allergic asthma. Understanding what component(s) of this exposure is responsible for this protection is crucial to understanding allergic asthma pathogenesis and developing strategies to prevent or treat allergic asthma. In this review, we introduce the concept of Farm-Friends, or specific microbes associated with both a farm environment and protection from allergic asthma. We review the mechanism(s) by which these Farm-Friends suppress allergic inflammation, with a focus on the molecule(s) produced by these Farm-Friends. Finally, we discuss the relevance of Farm-Friend administration (oral vs. inhaled) for preventing the development and severity of allergic asthma throughout childhood and adulthood. By developing a fuller understanding of which Farm-Friends modulate host immunity, a greater wealth of prophylactic and therapeutic options becomes available to counter the current allergy epidemic.

Asthma, a chronic respiratory condition that has seen a dramatic rise in prevalence over the past few decades, now affects more than 300 million people globally and imposes a significant burden on healthcare systems. The key pathological features of asthma include inflammation, airway hyperresponsiveness, mucus cell metaplasia, smooth muscle hypertrophy, and subepithelial fibrosis. Cytokines released by lung epithelial cells, stromal cells, and immune cells during asthma are critical to pathological tissue remodeling in asthma. Over the past few decades, researchers have made great strides in understanding key cells involved in asthma and the cytokines that they produce. Epithelial cells as well as many adaptive and innate immune cells are activated by environmental signals to produce cytokines, namely, type 2 cytokines (IL-4, IL-5, IL-13), IFN-γ, IL-17, TGF-β, and multiple IL-6 family members. However, the precise mechanisms through which these cytokines contribute to airway remodeling remain elusive. Additionally, multiple cell types can produce the same cytokines, making it challenging to decipher how specific cell types and cytokines uniquely contribute to asthma pathogenesis. This review highlights recent advances and provides a comprehensive overview of the key cells involved in the production of cytokines and how these cytokines modulate airway remodeling in asthma.

Asthma is a common chronic inflammatory disease of the airways. A substantial number of patients present with severe and therapy-resistant asthma, for which the underlying biological mechanisms remain poorly understood. In most asthma patients, airway inflammation is characterized by chronic activation of type 2 immunity. CD4⁺ T helper 2 (Th2) cells are the canonical producers of the cytokines that fuel type 2 inflammation: interleukin (IL)-4, IL-5, IL-9, and IL-13. However, more recent findings have shown that other lymphocyte subsets, in particular group 2 innate lymphoid cells (ILC2s) and type 2 CD8⁺ cytotoxic T (Tc2) cells, can also produce large amounts of type 2 cytokines. Importantly, a substantial number of severe therapy-resistant asthma patients present with chronic type 2 inflammation, despite the high sensitivity of Th2 cells for suppression by corticosteroids—the mainstay drugs for asthma. Emerging evidence indicates that ILC2s and Tc2 cells are more abundant in severe asthma patients and can adopt corticosteroid-resistance states. Moreover, many severe asthma patients do not present with overt type 2 airway inflammation, implicating non-type 2 immunity as a driver of disease. In this review, we will discuss asthma pathophysiology and focus on the roles played by ILC2s, Tc2 cells, and non-type 2 lymphocytes, placing special emphasis on severe disease forms.

Chronic lung diseases including asthma are characterized by an abnormal immune response and active tissue remodeling. These changes in the architecture of the tissue are a fundamental part of the pathology across the life course of patients suffering from asthma. Current treatments aim at dampening the immune system hyperactivation, but effective drugs targeting stromal or acellular structures are still lacking. This is mainly due to the lack of a detailed understanding of the composition of the large airways and the cellular interactions taking place in this niche. We and others have revealed multiple aspects of the spatial architecture of the airway wall in response to airborne insults. In this review, we discuss four elements that we believe should be the focus of future asthma research across the life course, to increase understanding and improve therapies: (i) specialized lung niches, (ii) the 3D architecture of the epithelium, (iii) the extracellular matrix, and (iv) the vasculature. These components comprise the main stromal structures at the airway wall, each playing a key role in the development of asthma and directing the immune response. We summarize promising future directions that will enhance lung research, ultimately benefiting patients with asthma.