Biology subjects

Josyula, A.

Publications and source records attributed to Josyula, A..

4 recordsLinked to original sources

bioRxiv2025

Damage signals preferentially activate killer CD8+/- regulatory T cells to protect injured tissue

Self-antigens that are obscure to immune cells under homeostasis, are exposed following tissue damage and can trigger autoimmunity. Our previous work showed that conventional type 1 dendritic cells (cDC1s) mediate immunoregulation after traumatic skeletal muscle injury. Here, we found that, immune responses to injury in cDC1-depleted mice (Batf3-/-) mirror those of autoimmune mice (Aire-/-). Mechanistically, we determined that cDC1s prime killer regulatory T cells (CD8+/-Ly49+Tregs) which express Ly49 inhibitory receptors and HELIOS. These killer-like Tregs are clonally diverse and carry T cell receptors associated with self-reactivity and response to hydrophobicity. cDC1 or CD8 deletion promoted CD62L+CCR7+ naive T cell retention and B cell recruitment to injured muscle. These naive T cells, which are implicated in autoimmunity, strongly correlate with B cell abundance in the muscle and are selectively pruned by CD8+/-Ly49+ Tregs. Furthermore, clinically used materials that promote wound healing enrich CD8+/-Ly49+ Treg function whereas those that are associated with pathology promote naive T cell and B cell accumulation. We hypothesize that CD8+/-Ly49+ Tregs maintain self-tolerance after tissue damage and avert autoimmunity by eliminating naive T cells and preventing pathogenic B cell activation.

immunology↗

bioRxiv2023

Ectopic adipogenesis in response to injury and material implantation in an autoimmune mouse model

Due to the limited capacity of mammals to regenerate complex tissues, researchers have worked to understand the mechanisms of tissue regeneration in organisms that maintain that capacity. One example is the MRL/MpJ mouse strain with unique regenerative capacity in ear pinnae that is absent from other strains, such as the common C57BL/6 strain. The MRL/MpJ mouse has also been associated with an autoimmune phenotype even in the absence of the mutant Fas gene described in its parent strain MRL/lpr. Due to these findings, we evaluated the differences between the responses of MRL/MpJ versus C57BL/6 strain in traumatic muscle injury and subsequent material implantation. One salient feature of the MRL/MpJ response to injury was a robust adipogenesis within the muscle. This was associated with a decrease in M2-like polarization in response to biologically derived extracellular matrix scaffolds. In pro-fibrotic materials, such as polyethylene, there were fewer foreign body giant cells in the MRL/MpJ mice. As there are reports of both positive and negative influences of adipose tissue and adipogenesis on wound healing, this model could provide an important lens to investigate the interplay between stem cells, adipose tissue, and immune responses in trauma and materials implantation.

bioengineering↗

bioRxiv2023

Conserved and tissue-specific immune responses to biologic scaffold implantation

1.Upon implantation into a patient, any biomaterial induces a cascade of immune responses that influences the outcome of that device. This cascade depends upon several factors, including the composition of the material itself and the location in which the material is implanted. There is still significant uncertainty around the role of different tissue microenvironments in the immune response to biomaterials and how that may alter downstream scaffold remodeling and integration. In this study, we present a study evaluating the immune response to decellularized extracellular matrix materials within the intraperitoneal cavity, the subcutaneous space, and in a traumatic skeletal muscle injury microenvironment. All different locations induced robust cellular recruitment, specifically of macrophages and eosinophils. The latter was most prominent in the subcutaneous space. Intraperitoneal implants uniquely recruited B cells that may alter downstream reactivity as adaptive immunity has been strongly implicated in the outcome of scaffold remodeling. These data suggest that the location of tissue implants should be taken together with the composition of the material itself when designing devices for downline therapeutics.

bioengineering↗

bioRxiv2022

The CD103-XCR1 axis mediates the recruitment of immunoregulatory dendritic cells after traumatic injury

During wounding and material implantation there is a disturbance in tissue homeostasis and release of self-antigen, and regulation between tolerance and auto-inflammation in injury is not well understood. Here, we analyzed antigen-presenting cells in biomaterial-treated muscle injury and found that pro-regenerative materials enrich Batf3-dependent CD103+XCR1+CD301b+ dendritic cells associated with cross-presentation and self-tolerance. Muscle trauma was accompanied by CD8+ iTregs and expansion of CD103+XCR1+CD62L- adaptive immune cells. Up-regulation of E-Cadherin (the ligand for CD103) and XCL-1 in injured tissue suggests a mechanism for cell recruitment to trauma. Without cross-presenting cells T cell activation increases, pro-regenerative macrophage polarization decreases, and muscle healing is impaired. These data describe a regulatory communication network through CD103+XCR1+ immune cells resulting in downstream effects on tissue regeneration.

bioengineering↗