https://dspace.nii.res.in//https://dspace.nii.res.in/handle/123456789/135 2026-04-27T15:59:40Z 2026-04-27T15:59:40Z Pal, Rahul Sharma, Hritika Bose, Anjali Sachdeva, Ruchi Malik, Monika Kumar, Uma https://dspace.nii.res.in//https://dspace.nii.res.in/handle/123456789/1281 2025-12-05T12:45:32Z 2022-01-01T00:00:00Z

Title: Haemoglobin drives inflammation and initiates antigen spread and nephritis in lupus Authors: Pal, Rahul; Sharma, Hritika; Bose, Anjali; Sachdeva, Ruchi; Malik, Monika; Kumar, Uma Abstract: Haemoglobin (Hb) has well-documented inflammatory effects and is normally efficiently scavenged; clearance mechanisms can be overwhelmed during erythrocyte lysis. Whether Hb is preferentially inflammatory in lupus and triggers broad anti-self responses was assessed. Peripheral blood mononuclear cells (PBMCs) derived from SLE patients secreted higher levels of lupus-associated inflammatory cytokines when incubated with human Hb than did PBMCs derived from healthy donors, an effect negated by haptoglobin. Ferric murine Hb triggered the preferential release of lupus-associated cytokines from splenocytes, B cells, CD4 T cells, CD8 T cells and plasmacytoid dendritic cells isolated from ageing, lupus-prone NZM2410 mice, and also had mitogenic effects on B cells. Pull-downs, followed by mass spectrometry, revealed interactions of Hb with several lupus-associated autoantigens; co-incubation of ferric Hb with apoptotic blebs (structures that contain packaged autoantigens) revealed synergies-in terms of cytokine release and autoantibody production in vitro-that were also restricted to the lupus genotype. Murine ferric Hb activated multiple signalling pathways and, in combination with apoptotic blebs, preferentially triggered MAP kinase signalling specifically in splenocytes isolated from lupus-prone mice. Infusion of murine ferric Hb into lupus-prone mice led to enhanced release of lupus-associated cytokines, the generation of a spectrum of autoantibodies and enhanced-onset glomerulosclerosis. Given that the biased recognition of ferric Hb in a lupus milieu, possibly in concert with lupus-associated autoantigens, triggers inflammatory responses and the generation of lupus-associated cytokines, and also stimulates the generation of potentially pathogenic lupus-associated autoantibodies, neutralization of Hb could have beneficial effects.

2022-01-01T00:00:00Z Pal, Rahul Soni, Kapil Dev Aggarwal, Richa Malhotra, Rajesh Mathur, Purva Khurana, Surbhi Bhardwaj, Nidhi Kumar, Subodh Sagar, Sushma https://dspace.nii.res.in//https://dspace.nii.res.in/handle/123456789/1280 2025-12-05T12:45:41Z 2020-01-01T00:00:00Z

Title: Crosstalk between T Helper Cell Subsets and Their Roles in Immunopathogenesis and Outcome of Polytrauma Patients Authors: Pal, Rahul; Soni, Kapil Dev; Aggarwal, Richa; Malhotra, Rajesh; Mathur, Purva; Khurana, Surbhi; Bhardwaj, Nidhi; Kumar, Subodh; Sagar, Sushma Abstract: Purpose: One of the leading causes of morbidity and early-age mortality across the globe is trauma. It disrupts immune system homeostasis and intensely affects the innate and adaptive immune responses, predisposing patients to posttrauma complications and poor outcomes. Most of the studies on posttrauma cellular immune response have been centered on the T helper-1-T helper-2 imbalances after trauma. This study was conducted to understand the role of circulating novel T helper cells in the acute posttraumatic period and clinical outcome of trauma patients. Materials and methods: Signature cytokines and transcription factors of circulating Th (T helper)-9, Th-17, Th-22, and regulatory T helper cells were studied using flowcytometry along with serum biomarkers in 49 patients with polytraumatic injuries admitted to a tertiary care hospital. The patients were followed up until their outcome. The results were correlated with their clinical outcomes. Results: In patients who died, higher nTreg, iTreg, Tr1 (early-phase), and higher IRF4+Th-9, IL17+ Th-17, and RORγT+ Th-17 (mid-phase) were seen. However, by the late phase, only RORγT+ Th-17 remained higher. Serum IL-6 and PCT were found to be consistently higher. In survivors, higher Th-3 (early phase), Th-22 (mid-phase), and IRF4+Th-9, IL17+ Th-17, nTreg, Th-3 (late phase) were observed to have played a protective role. Serum IL-2, IL-4, IL-17A and IL-22 were significantly higher in survivors. Conclusion: Different T helper subsets were observed to be playing pathogenic and protective roles in different phases of trauma and could be used for early prognostication and make way for noninvasive management of critically injured trauma patients by immunomodulation. How to cite this article: Khurana S, Bhardwaj N, Kumar S, Sagar S, Pal R, Soni KD, et al. Crosstalk between T Helper Cell Subsets and Their Roles in Immunopathogenesis and Outcome of Polytrauma Patients. Indian J Crit Care Med 2020;24(11):1037-1044.

2020-01-01T00:00:00Z Pal, Rahul Huhtaniemi, Ilpo Agrawal, Usha Sarkar, Moumita Singh, Poonam https://dspace.nii.res.in//https://dspace.nii.res.in/handle/123456789/1055 2025-12-05T12:43:37Z 2018-01-01T00:00:00Z

Title: The transgenic expression of the β-subunit of human chorionic gonadotropin influences the growth of implanted tumor cells Authors: Pal, Rahul; Huhtaniemi, Ilpo; Agrawal, Usha; Sarkar, Moumita; Singh, Poonam Abstract: The beta subunit of human chorionic gonadotropin (βhCG) is secreted by various tumors, and its presence associated with poor prognosis. Though exogenous hCG elicits the synthesis of molecules associated with angiogenesis, invasion, immune suppression and chemoresistance from responsive tumor cells in vitro, the influence of cell-extrinsic βhCG on tumorigenesis in vivo has not been adequately explored. Female C57BL/6-/- × FVBβhCG/- F1 transgenic mice demonstrated ovarian hyperplasia and pituitary adenomas; transcripts of hCG-driven, tumor-associated molecules were heightened in the pituitary. Upon the implantation of Lewis Lung Carcinoma cells (murine lung tumor cells derived from C57BL/6 mice) in transgenic mice, tumor incidence and volume were enhanced, and increased transcription and expression of hCG-driven, tumor-associated molecules was observed in excised tumors. While treatment of these mice with Cabergoline (a potent dopamine receptor agonist) had no significant effects, ovariectomy resulted in a reduction in the lag phase, accompanied by an increase in tumor incidence and volume upon Lewis Lung Carcinoma cell implantation. In tumors derived from Lewis Lung Carcinoma cell-implanted ovariectomized, transgenic mice, the transcription and expression of hCG-driven, tumor-associated molecules remained elevated and enhanced animal mortality was observed. Cell-extrinsic βhCG can therefore induce pro-tumorigenic effects in vivo (even on tumor lineages not part of the reproductive axis), with ovarian products mediating an ameliorating influence.

2018-01-01T00:00:00Z Pal, Rahul Sachdeva, Ruchi De, Alpana Malik, Monika Bose, Anjali Jayachandran, Nipun https://dspace.nii.res.in//https://dspace.nii.res.in/handle/123456789/1054 2025-12-05T12:43:23Z 2018-01-01T00:00:00Z

Title: Human Chorionic Gonadotropin Influences Systemic Autoimmune Responses Authors: Pal, Rahul; Sachdeva, Ruchi; De, Alpana; Malik, Monika; Bose, Anjali; Jayachandran, Nipun Abstract: Immunopathological outcomes in Systemic Lupus Erythematosus (SLE; or lupus) are believed to be autoantibody-mediated. Conditions which promote a Th2 skew (such as pregnancy) should encourage antibody production, worsening antibody-mediated diseases while ameliorating Th1/Th17-mediated diseases. Although an increased propensity toward autoreactivity can be observed in pregnant lupus patients and in pregnant lupus-prone mice, whether a unique human pregnancy-specific factor can contribute to such effects is unknown. This study assessed whether human chorionic gonadotropin (hCG, a pregnancy-specific hormone of diverse function) at physiological concentrations could mediate stimulatory influences on immune parameters in non-pregnant, lupus-prone mice, in light of the hormone's ameliorating effects on Th1-mediated autoimmunity in murine models. Results demonstrate that administration of hCG heightened global autoreactivity in such mice; antibodies to dsDNA, RNP68, Protein S, Protein C, β2-glycoprotein 1, and several phospholipids were enhanced, and hormone administration had adverse effects on animal survival. Specifically in splenic cell cultures containing cells derived from lupus-prone mice, hCG demonstrated synergistic effects with TLR ligands (up-modulation of costimulatory markers on B cells) as well as with TCR stimuli (enhanced proliferative responses, enhanced levels of cytokines, and the phosphorylation of p38). In both instances, enhanced synthesis of lupus-associated cytokines was observed, in addition to the heightened generation of autoantibodies reactive toward apoptotic blebs. These results suggest that selective transducive, proliferative, and differentiative effects of hCG on adaptive immune cells may drive autoreactive responses in a lupus environment, and may also potentially provide insights into the association between the presence of higher hCG levels (or the administration of hCG) with the presence (or appearance) of humoral autoimmunity.

2018-01-01T00:00:00Z