Novel Therapies for Autoimmune Diseases

Technology Overview

Dr. Mridu Acharya

In a healthy immune system, B cells produce antibodies that recognize foreign invaders such as viruses or bacteria while avoiding the body’s own tissues. In autoimmune diseases, however, this normal tolerance breaks down and B cells can begin recognizing and responding to the body’s own molecules, which are known as self-antigens. This process can lead to chronic inflammation and tissue damage.

In addition to producing antibodies, B cells also help direct immune responses by taking up proteins from pathogens or damaged tissues, breaking them down into smaller pieces, and displaying these pieces to T cells. This process, called antigen presentation, helps activate T cells and shape the broader adaptive immune response. Increasing evidence suggests that in autoimmune diseases, B cells can present self-antigens to T cells, driving harmful immune activation. As a result, B cells contribute to autoimmune disease not only through autoantibody production, but also likely by promoting pathogenic T cell responses.

Immunologist Mridu Acharya, PhD, and collaborators discovered that integrins, which are transmembrane proteins with structural and cell-signaling functions, are involved in B-cell activation. Specifically, integrins influence Toll-like receptor (TLR) signaling that promotes B cell maturation, proliferation and antibody production. In animal models of the most common form of lupus, systemic lupus erythematosus (SLE), TLR signaling in B cells has been linked to production of self-directed antibodies, and thus researchers think that targeting B-cell integrins could lead to treatments for human autoimmune diseases.

In vivo evidence from Dr. Acharya’s work supports the connections among integrins, TLR signaling, and autoimmunity. Dr. Acharya’s group found that deleting the αv integrin (for integrin alpha chain V) from B cells in an animal model makes B cells hyperresponsive, resulting in the B cells producing more antibodies. As the B-cell integrin-knockout animals age, they develop signs of autoimmunity, such as production of self-directed antibodies against double-stranded DNA.

These findings indicate that αv integrins normally act as a regulatory “brake” that helps prevent self-reactive B cells from becoming activated. Mechanistic studies revealed that αv integrins cooperate with components of the autophagy machinery, including ATG5 and LC3 proteins, to regulate intracellular trafficking pathways that control B cells. Polymorphisms in the human autophagy genes such ATG5 and ATG7 have been linked to SLE, supporting the idea that defects in intracellular trafficking pathways could contribute to loss of immune tolerance and autoimmune disease.

Building on these discoveries, the Acharya Lab is now investigating how intracellular trafficking pathways inside B cells control the handling and processing of self-antigens and microbial antigens. A major focus of the laboratory is understanding how these pathways determine where antigens travel within B cells, how antigens are presented to T cells, and how disruptions in these processes can drive abnormal T cell activation in autoimmune diseases such as SLE and type 1 diabetes (T1D). This work aims to uncover fundamental mechanisms shared across multiple autoimmune diseases and identify pathways that could be therapeutically targeted to selectively restrain harmful immune responses.

To extend these discoveries into human systems, the Acharya Lab is also developing engineered human B-cell platforms in collaboration with pediatric immunologists Richard James, PhD, and David Rawlings, MD. These studies combine antigen-specific human B and T cells, gene-editing approaches, and advanced imaging technologies to directly examine how human B cells process and present self-antigens to T cells. The platform is designed to reveal new mechanisms regulating autoreactive immune responses and accelerate development of precision therapies for autoimmune disease.

Dr. Acharya is currently screening small molecules that modulate integrin function or alter how B cells process different types of antigens. Potential applications of these candidate compounds include boosting beneficial B-cell responses to vaccines or reducing harmful B- and T-cell activation in autoimmune disease. Dr. Acharya is interested in partnerships to further this drug discovery and development work.

Stage of Development

• Preclinical in vitro
• Preclinical in vivo

Partnering Opportunities

• Collaborative research opportunity
• Sponsored research agreement
• Consultation agreement

Learn More

• Mridu Acharya, PhD
• Acharya Lab

Publications

1. Lagos J, Holder U, Sagadiev S … Acharya M. B cell adapter for PI 3-kinase (BCAP) coordinates antigen internalization and trafficking through the B cell receptor. Sci Adv. 2024;10(46):eadp1747.
2. Muir V, Sagadiev S, Liu S … Acharya M. Transcriptomic analysis of pathways associated with ITGAV/alpha(v) integrin-dependent autophagy in human B cells. Autophagy. 2023;19(3):926-942.
3. Acharya M, Jackson SW. Regulatory strategies limiting endosomal Toll-like receptor activation in B cells. Immunol Rev. 2022;307(1):66-78.
4. Acharya M, Raso F, Sagadiev S, et al. B cell αv integrins regulate TLR-driven autoimmunity. J Immunol. 2020;205(7):1810-1818.
5. Acharya M, Sokolovska A, Tam JM, et al. αv Integrins combine with LC3 and atg5 to regulate Toll-like receptor signalling in B cells. Nat Commun. 2016;7:10917.
6. Edkins AL, Borland G, Acharya M, et al. Differential regulation of monocyte cytokine release by αV and β(2) integrins that bind CD23. Immunol. 2012;136(2):241-251

Last updated June 11, 2026