Modulating Lymph Node Immune Homeostasis via Sensory Neuron Gene Expression
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Solution Overview
Problem
The immune system's ability to modulate immune responses and homeostasis in lymph nodes (LNs) is not fully understood, particularly how LN-innervating sensory neurons contribute to these processes, due to a lack of systematic understanding of their structural, molecular, and functional architecture, and the absence of definitive markers for nonpeptidergic sensory neurons.
Innovation Solution
Administering agents that modulate the expression or function of specific genes in LN-innervating peptidergic nociceptor sensory neurons, such as those characterized by the expression of Trpc4, Trpm8, Kchnh5, and Ache, to influence neural stimulation and efferent signaling, and interacting with lymphatic endothelial cells and other stromal cells to regulate immune responses and homeostasis.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Loss of information
If traditional anatomic and functional characterization methods are used to study sensory neuron-immune interactions, then general understanding of immune responses can be obtained, but systematic understanding of structural, molecular and functional architecture of LN-innervating sensory neurons cannot be achieved
Solution Approach 1:
The patent segments the study of sensory neurons into distinct populations based on peptidergic (CGRP+) and nonpeptidergic (CGRP-) classification. This segmentation allows systematic characterization of each population's molecular profile, innervation patterns, and immunomodulatory functions separately, thereby achieving comprehensive understanding without overwhelming complexity
Solution Approach 2:
The patent uses specific molecular markers (CGRP, Substance P, TRPV1, etc.) as intermediaries to identify and characterize sensory neuron populations. These molecular mediators enable systematic differentiation and functional analysis of diverse sensory neuron types innervating lymph nodes, bridging the gap between anatomical structure and immune function
2Loss of information
If nociceptors are globally ablated to study immune responses, then overall immunological consequences can be observed, but tissue-specific local sensory neuron-immune circuits cannot be dissected
Solution Approach 1:
The patent applies local quality by focusing specifically on lymph node-innervating sensory neurons rather than globally studying all sensory neurons. By isolating and characterizing the molecular and functional properties of LN-specific sensory neuron populations, the patent enables tissue-specific dissection of neuroimmune circuits while maintaining methodological feasibility
Solution Approach 2:
The patent changes the parameter of spatial localization by defining sensory neurons based on their innervation target (lymph node vs. other tissues). This parameter change allows selective study of LN-innervating populations through anatomical tracing and molecular profiling, enabling tissue-specific analysis without requiring complex selective manipulation techniques
3Measurement precision
If peptidergic markers are used to identify sensory neurons, then CGRP+ populations can be characterized, but nonpeptidergic sensory neurons lack definitive markers for identification
Solution Approach 1:
The patent inverts the traditional approach by not only characterizing peptidergic (CGRP+) neurons but also systematically defining nonpeptidergic (CGRP-) sensory neurons through molecular profiling. This inversion allows precise identification of both populations using complementary marker sets, achieving comprehensive measurement precision without excessive complexity
Solution Approach 2:
The patent establishes a universal molecular framework that identifies sensory neurons through multiple functional markers (neuropeptides, ion channels, receptors) that can apply to both peptidergic and nonpeptidergic populations. This multi-functional marker system enables precise identification across diverse neuronal types while maintaining a unified, manageable identification framework
Data Source
AI summary
The present invention discloses novel methods, uses thereof, and compositions for modulating immune responses and homeostasis in a lymph node (LN). Moreover, structural and molecular characteristics of LN-innervating sensory neurons are provided. The present invention also discloses the target cells for LN-innervating sensory neurons in LN and molecular profiles of these target cells. These molecular characteristics provide therapeutic targets for modulating immune response and immune homeostasis in LN in an animal or a human.