Related Experiment Video
Updated: Aug 6, 2026
10:39
In Vitro Analysis of Myd88-mediated Cellular Immune Response to West Nile Virus Mutant Strain Infection
Published on: November 27, 2014
MyD88-Family Adaptors: Compartmentalised Signalling and Non-Immune Functions
Seshu Vardhan Pothabathula1,2,3, Saurabh Mishra1,2,3, Pugazhendhi Kannan1,2,3
1Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA.
Immunology
|August 5, 2026
Summary
The MyD88 protein family, crucial for innate immunity, also regulates non-immune tissue functions. Adaptor proteins like MyD88 and SARM1 control diverse physiological processes and disease responses.
Area of Science:
- Immunology
- Cell Biology
- Physiology
Background:
- The MyD88 (myeloid differentiation primary response protein 88) family of Toll/interleukin-1 receptor (TIR) domain-containing adaptor proteins are central to innate immunity.
- These adaptors integrate immune sensing with stress responses, classically studied in immune cells.
- Emerging evidence highlights their critical roles in non-immune tissues.
Purpose of the Study:
- To synthesize structural, genetic, and cell-specific studies on MyD88-family adaptors.
- To elucidate how compartmentalized adaptor usage and domain-specific mechanisms generate context-dependent signaling outcomes.
- To redefine MyD88-family adaptors as modular regulators of tissue physiology and disease.
Main Methods:
- Review of structural, genetic, and cell-specific studies.
- Analysis of canonical and non-canonical signaling pathways.
- Integration of findings across immune and non-immune tissues.
Main Results:
- MyD88 adaptors (MyD88, TIRAP/MAL, TRIF/TICAM-1, TRAM/TICAM-2, SARM1) have critical functions beyond immunity.
- Signaling pathways regulate epithelial integrity, metabolism, muscle function, and neuronal degeneration.
- SARM1 acts as an NAD+ hydrolase, driving axonal degeneration.
Conclusions:
- MyD88-family adaptors are modular regulators of tissue physiology and disease.
- Context-dependent signaling arises from compartmentalized usage and domain mechanisms.
- These insights have implications for targeted therapeutic interventions.
Related Concept Videos
01:26Antigens Involved in Adaptive Immunity
An antigen is any substance the immune system identifies as foreign and potentially harmful to the body, prompting an immune response. Antigens have two functional properties: immunogenicity and reactivity. Immunogenicity is the ability of an antigen to stimulate a specific immune response. At the same time, reactivity describes the antigen's ability to react with the cells and antibodies produced in response to it.
Complete Antigens
Complete antigens possess both immunogenicity and reactivity.
Complete Antigens
Complete antigens possess both immunogenicity and reactivity.
01:28Diversity of Antigen Receptors
Antigen receptors are essential components of the immune system crucial in defending the body against foreign invaders. These receptors are present on the surface of B and T cells, enabling them to recognize antigens and mount an appropriate immune response.
Before encountering any antigen, lymphocytes express these receptors. On B cells, the antigen receptor is a membrane-bound antibody molecule called BCR; on T cells, it is a T cell receptor or TCR. B and T cell receptors are composed of two...
Before encountering any antigen, lymphocytes express these receptors. On B cells, the antigen receptor is a membrane-bound antibody molecule called BCR; on T cells, it is a T cell receptor or TCR. B and T cell receptors are composed of two...
01:40Cell-mediated Immune Responses
Overview
01:24B Cell Activation and Differentiation
The adaptive immune response, a sophisticated defense mechanism, relies on the activation and differentiation of B lymphocytes, or B cells. These processes enable our bodies to mount a tailored response against specific pathogens such as bacteria, free virus particles, toxins, and parasites.
When naive B cells encounter a specific antigen that can bind to the B cell receptor (BCR) on their surface, they undergo sensitization to respond to the antigen's presence. Sensitization begins with...
When naive B cells encounter a specific antigen that can bind to the B cell receptor (BCR) on their surface, they undergo sensitization to respond to the antigen's presence. Sensitization begins with...
01:31Antigen Processing Pathways
MHC molecules are key players in the immune response, enabling T cells to recognize and respond to specific antigens. They are present on the surface of all nucleated cells in the body and are instrumental in presenting antigens to T cells and activating them. T cells recognize the MHC-antigen complex and initiate an immune response. MHC class I and MHC class II are two main types of MHC molecules, each associated with a distinct antigen processing pathway.
MHC Class I: Presenting Endogenous...
MHC Class I: Presenting Endogenous...
01:20Special Features of Adaptive Immunity
The adaptive immune system, a crucial component of the overall immune response, offers a highly specialized defense against pathogens. It involves specific cell types and features, enabling it to combat infections effectively and efficiently.
The primary cell types involved in adaptive immunity are T cells and B cells. Each type has a unique role in defending the body against pathogens. T cells are responsible for cell-mediated immunity. They identify and eliminate infected cells directly,...
The primary cell types involved in adaptive immunity are T cells and B cells. Each type has a unique role in defending the body against pathogens. T cells are responsible for cell-mediated immunity. They identify and eliminate infected cells directly,...