Immune responses must be rapid, tightly orchestrated, and tailored to the encountered stimulus. Lymphatic vessels facilitate this process by continuously collecting immunological information (ie, antigens, immune cells, and soluble mediators) about the current state of peripheral tissues, and transporting these via the lymph across the lymphatic system. Lymph nodes (LNs), which are critical meeting points for innate and adaptive immune cells, are strategically located along the lymphatic network to intercept this information. Within LNs, immune cells are spatially organized, allowing them to efficiently respond to information delivered by the lymph, and to either promote immune homeostasis or mount protective immune responses. These responses involve the activation and functional cooperation of multiple distinct cell types and are tailored to the specific inflammatory conditions. The natural patterns of lymph flow can also generate spatial gradients of antigens and agonists within draining LNs, which can in turn further regulate innate cell function and localization, as well as the downstream generation of adaptive immunity. In this review, we explore how information transmitted by the lymph shapes the spatiotemporal organization of innate and adaptive immune responses in LNs, with particular focus on steady state and Type‐I vs. Type‐II inflammation.
Microanatomical organization of innate immune cells within lymph nodes (LNs) is critical for the generation of adaptive responses. In particular, steady-state LN-resident dendritic cells (Res cDCs) are strategically localized to intercept lymph-draining antigens. Whether myeloid cell organization changes during inflammation and how that might affect the generation of immune responses are unknown. Here, we report that during type I, but not type II, inflammation after adjuvant immunization or viral infection, antigen-presenting Res cDCs undergo CCR7-dependent intranodal repositioning from the LN periphery into the T cell zone (TZ) to elicit T cell priming. Concurrently, inflammatory monocytes infiltrate the LNs via local blood vessels, enter the TZ, and cooperate with Res cDCs by providing polarizing cytokines to optimize T cell effector differentiation. Monocyte infiltration is nonuniform across LNs, generating distinct microenvironments with varied local innate cell composition. These spatial microdomains are associated with divergent early T cell effector programming, indicating that innate microenvironments within LNs play a critical role in regulating the quality and heterogeneity of T cell responses. Together, our findings reveal that dynamic modulation of innate cell microenvironments during type I inflammation leads to optimized generation of adaptive immune responses to vaccines and infections.
more » « less- PAR ID:
- 10214375
- Publisher / Repository:
- American Association for the Advancement of Science (AAAS)
- Date Published:
- Journal Name:
- Science Immunology
- Volume:
- 6
- Issue:
- 56
- ISSN:
- 2470-9468
- Page Range / eLocation ID:
- Article No. eabb9435
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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