{"id":{"repo_id":"houston","oai_identifier":"oai:uh-ir.tdl.org:10657/21482"},"canonical_url":"https://search.dev.ndltd.org/etd/houston/oai:uh-ir.tdl.org:10657/21482","repository":{"repo_id":"houston","name":"University of Houston","base_url":"https://uh-ir.tdl.org/server/oai/request"},"display":{"title":"M2 Polarization and Pro-Fibrotic Transition of Lupus Nephritis Macrophages","abstract":"Chronic inflammation is a defining feature of autoimmune diseases, such as lupus nephritis (LN), in which persistent immune activation leads to progressive kidney injury and fibrosis. Macrophages play a central role in this process because of their functional plasticity and ability to respond to environmental cues. Classically activated M1 macrophages promote inflammation through cytokines such as IL-1β, IL-6, and TNF-α, whereas alternatively activated M2 macrophages support immune regulation and tissue repair processes. However, in LN, increased infiltration of CD163⁺ M2 macrophages is associated with disease severity and fibrotic remodeling, suggesting that sustained reparative signaling may contribute to the pathology. Macrophage polarization is strongly influenced by the cytokine milieu. Canonical Th2 cytokines, including IL-4 and IL-13, drive M2 differentiation via STAT6 signaling, whereas IL-10 suppresses inflammation via STAT3 and enhances M2 marker expression. As these cytokines often coexist in chronic inflammation, we investigated whether their combined action promotes a more stable M2 phenotype than individual stimulation. Using THP-1–derived macrophages, we evaluated the role of non-canonical Th2-associated mediators, including CXCL1, CCL11, IL-6, IL-9, and TSLP, in shaping macrophage function within the LN microenvironment. To determine whether macrophages contribute directly to fibrosis, we examined the effects of TGF-β and LN patient serum on macrophage reprogramming. Renal biopsy transcriptomic analysis revealed increased expression of fibrotic markers, including vimentin, collagen I, collagen IV, and fibronectin in LN glomeruli. In vitro, TGF-β induced a dose- and time-dependent increase in fibroblast-associated markers, including α-smooth muscle actin and fibroblast-specific protein-1, indicating the acquisition of a myofibroblast-like phenotype. LN serum similarly promoted both M2 polarization and profibrotic gene expression, demonstrating that circulating lupus factors drive macrophage-mediated tissue remodeling. Finally, we propose a CRISPR-Cas9–based screening of membrane proteins to identify key receptors mediating macrophage responses to LN-associated stimuli. Together, these findings highlight macrophages as active drivers of fibrosis and provide insights into how Th2 cytokine signaling and systemic inflammatory factors contribute to progressive tissue damage in LN.","abstract_html":"Chronic inflammation is a defining feature of autoimmune diseases, such as lupus nephritis (LN), in which persistent immune activation leads to progressive kidney injury and fibrosis. Macrophages play a central role in this process because of their functional plasticity and ability to respond to environmental cues. Classically activated M1 macrophages promote inflammation through cytokines such as IL-1β, IL-6, and TNF-α, whereas alternatively activated M2 macrophages support immune regulation and tissue repair processes. However, in LN, increased infiltration of CD163⁺ M2 macrophages is associated with disease severity and fibrotic remodeling, suggesting that sustained reparative signaling may contribute to the pathology. Macrophage polarization is strongly influenced by the cytokine milieu. Canonical Th2 cytokines, including IL-4 and IL-13, drive M2 differentiation via STAT6 signaling, whereas IL-10 suppresses inflammation via STAT3 and enhances M2 marker expression. As these cytokines often coexist in chronic inflammation, we investigated whether their combined action promotes a more stable M2 phenotype than individual stimulation. Using THP-1–derived macrophages, we evaluated the role of non-canonical Th2-associated mediators, including CXCL1, CCL11, IL-6, IL-9, and TSLP, in shaping macrophage function within the LN microenvironment. To determine whether macrophages contribute directly to fibrosis, we examined the effects of TGF-β and LN patient serum on macrophage reprogramming. Renal biopsy transcriptomic analysis revealed increased expression of fibrotic markers, including vimentin, collagen I, collagen IV, and fibronectin in LN glomeruli. In vitro, TGF-β induced a dose- and time-dependent increase in fibroblast-associated markers, including α-smooth muscle actin and fibroblast-specific protein-1, indicating the acquisition of a myofibroblast-like phenotype. LN serum similarly promoted both M2 polarization and profibrotic gene expression, demonstrating that circulating lupus factors drive macrophage-mediated tissue remodeling. Finally, we propose a CRISPR-Cas9–based screening of membrane proteins to identify key receptors mediating macrophage responses to LN-associated stimuli. Together, these findings highlight macrophages as active drivers of fibrosis and provide insights into how Th2 cytokine signaling and systemic inflammatory factors contribute to progressive tissue damage in LN.","abstract_has_math":false,"creators":["Biswas, Aalekhya Sharma"],"institution":"University of Houston","degree_name":"Doctor of Philosophy","degree_level":null,"degree_discipline":"Biology","degree_department":null,"school":null,"contributors":[],"advisors":["Mohan, Chandra"],"committee_chairs":[],"committee_members":["Titus, Anto Sam Crosslee Louis Sam","Wu, Tianfu","Peng, Weiyi","Lin, Chin-Yo"],"year":2026,"date_issued":"2026-05","date_published":"2026-05","updated_at":"2026-07-24T02:32:58Z","subjects":["M2 polarization","Cytokine synergy","LN serum treatment","CSRISPRa technology"],"languages":["English"],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://hdl.handle.net/10657/21482","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Mohan, Chandra"]},{"key":"dc:contributor.committeemember","label":"Committee Member","values":["Titus, Anto Sam Crosslee Louis Sam","Wu, Tianfu","Peng, Weiyi","Lin, Chin-Yo"]},{"key":"dc:creator","label":"Author","values":["Biswas, Aalekhya Sharma"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2026-07-13T17:20:47Z"]},{"key":"dc:date.issued","label":"Date","values":["2026-05"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Biology"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Doctor of Philosophy"]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["University of Houston"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["M2 polarization","Cytokine synergy","LN serum treatment","CSRISPRa technology"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language.iso","label":"Language (ISO)","values":["English"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://hdl.handle.net/10657/21482"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Chronic inflammation is a defining feature of autoimmune diseases, such as lupus nephritis (LN), in which persistent immune activation leads to progressive kidney injury and fibrosis. Macrophages play a central role in this process because of their functional plasticity and ability to respond to environmental cues. Classically activated M1 macrophages promote inflammation through cytokines such as IL-1β, IL-6, and TNF-α, whereas alternatively activated M2 macrophages support immune regulation and tissue repair processes. However, in LN, increased infiltration of CD163⁺ M2 macrophages is associated with disease severity and fibrotic remodeling, suggesting that sustained reparative signaling may contribute to the pathology. Macrophage polarization is strongly influenced by the cytokine milieu. Canonical Th2 cytokines, including IL-4 and IL-13, drive M2 differentiation via STAT6 signaling, whereas IL-10 suppresses inflammation via STAT3 and enhances M2 marker expression. As these cytokines often coexist in chronic inflammation, we investigated whether their combined action promotes a more stable M2 phenotype than individual stimulation. Using THP-1–derived macrophages, we evaluated the role of non-canonical Th2-associated mediators, including CXCL1, CCL11, IL-6, IL-9, and TSLP, in shaping macrophage function within the LN microenvironment. To determine whether macrophages contribute directly to fibrosis, we examined the effects of TGF-β and LN patient serum on macrophage reprogramming. Renal biopsy transcriptomic analysis revealed increased expression of fibrotic markers, including vimentin, collagen I, collagen IV, and fibronectin in LN glomeruli. In vitro, TGF-β induced a dose- and time-dependent increase in fibroblast-associated markers, including α-smooth muscle actin and fibroblast-specific protein-1, indicating the acquisition of a myofibroblast-like phenotype. LN serum similarly promoted both M2 polarization and profibrotic gene expression, demonstrating that circulating lupus factors drive macrophage-mediated tissue remodeling. Finally, we propose a CRISPR-Cas9–based screening of membrane proteins to identify key receptors mediating macrophage responses to LN-associated stimuli. Together, these findings highlight macrophages as active drivers of fibrosis and provide insights into how Th2 cytokine signaling and systemic inflammatory factors contribute to progressive tissue damage in LN."]},{"key":"dc:format.mimetype","label":"Dc Format Mimetype","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["M2 Polarization and Pro-Fibrotic Transition of Lupus Nephritis Macrophages"]}]}],"canonical_facts":{"dc:contributor.advisor":["Mohan, Chandra"],"dc:contributor.committeemember":["Titus, Anto Sam Crosslee Louis Sam","Wu, Tianfu","Peng, Weiyi","Lin, Chin-Yo"],"dc:creator":["Biswas, Aalekhya Sharma"],"dc:date.accessioned":["2026-07-13T17:20:47Z"],"dc:date.issued":["2026-05"],"dc:description.abstract":["Chronic inflammation is a defining feature of autoimmune diseases, such as lupus nephritis (LN), in which persistent immune activation leads to progressive kidney injury and fibrosis. Macrophages play a central role in this process because of their functional plasticity and ability to respond to environmental cues. Classically activated M1 macrophages promote inflammation through cytokines such as IL-1β, IL-6, and TNF-α, whereas alternatively activated M2 macrophages support immune regulation and tissue repair processes. However, in LN, increased infiltration of CD163⁺ M2 macrophages is associated with disease severity and fibrotic remodeling, suggesting that sustained reparative signaling may contribute to the pathology. Macrophage polarization is strongly influenced by the cytokine milieu. Canonical Th2 cytokines, including IL-4 and IL-13, drive M2 differentiation via STAT6 signaling, whereas IL-10 suppresses inflammation via STAT3 and enhances M2 marker expression. As these cytokines often coexist in chronic inflammation, we investigated whether their combined action promotes a more stable M2 phenotype than individual stimulation. Using THP-1–derived macrophages, we evaluated the role of non-canonical Th2-associated mediators, including CXCL1, CCL11, IL-6, IL-9, and TSLP, in shaping macrophage function within the LN microenvironment. To determine whether macrophages contribute directly to fibrosis, we examined the effects of TGF-β and LN patient serum on macrophage reprogramming. Renal biopsy transcriptomic analysis revealed increased expression of fibrotic markers, including vimentin, collagen I, collagen IV, and fibronectin in LN glomeruli. In vitro, TGF-β induced a dose- and time-dependent increase in fibroblast-associated markers, including α-smooth muscle actin and fibroblast-specific protein-1, indicating the acquisition of a myofibroblast-like phenotype. LN serum similarly promoted both M2 polarization and profibrotic gene expression, demonstrating that circulating lupus factors drive macrophage-mediated tissue remodeling. Finally, we propose a CRISPR-Cas9–based screening of membrane proteins to identify key receptors mediating macrophage responses to LN-associated stimuli. Together, these findings highlight macrophages as active drivers of fibrosis and provide insights into how Th2 cytokine signaling and systemic inflammatory factors contribute to progressive tissue damage in LN."],"dc:format.mimetype":["application/pdf"],"dc:identifier.uri":["https://hdl.handle.net/10657/21482"],"dc:language.iso":["English"],"dc:subject":["M2 polarization","Cytokine synergy","LN serum treatment","CSRISPRa technology"],"dc:title":["M2 Polarization and Pro-Fibrotic Transition of Lupus Nephritis Macrophages"],"dc:type":["Thesis"],"thesis:degree_discipline":["Biology"],"thesis:degree_name":["Doctor of Philosophy"],"thesis:institution_name":["University of Houston"]},"updated_at":"2026-07-24T02:32:58Z"}