Debdut Naskar - Academia.edu (original) (raw)

Papers by Debdut Naskar

Research paper thumbnail of Macrophage as a mediator of immune response: Sustenance of immune homeostasis

Macrophage, 2015

Macrophages have evolved as a key player in our immune system. As macrophages remain groomed to c... more Macrophages have evolved as a key player in our immune system. As macrophages remain groomed to combat invasions by pathogens they also exhibit distinct polarized (M1/M2) states while adapting to the local environmental milieu. Detailed molecular mechanisms governing the prevalence of the usual steady state as well as altered (M1/M2) homeostasis programs under normal and pathogenic conditions remain to be deciphered. In this review, we have discussed the significance of immune homeostasis in macrophages and the involvement of Wnt-Frizzled signalling therein. Overall this review throws light upon some important questions related to the immune homeostasis scheme, answers to which will offer new insight in the field of immunology.

Research paper thumbnail of Designing of RNA aptamer against DNA binding domain of the glucocorticoid receptor: A response element-based in-silico approach

Journal of Biomolecular Structure and Dynamics

Research paper thumbnail of Wnt Signaling: Pathogen Incursion and Immune Defense

Research paper thumbnail of Segmented Filamentous Bacteria Provoke Lung Autoimmunity by Inducing Gut-Lung Axis Th17 Cells Expressing Dual TCRs

Cell host & microbe, Nov 8, 2017

Lung complications are a major cause of rheumatoid arthritis-related mortality. Involvement of gu... more Lung complications are a major cause of rheumatoid arthritis-related mortality. Involvement of gut microbiota in lung diseases by the gut-lung axis has been widely observed, but the underlying mechanism remains mostly unknown. Using an autoimmune arthritis model, we show that a constituent of the gut microbiota, segmented filamentous bacteria (SFB), distantly provoke lung pathology. SFB induce autoantibodies in lung during the pre-arthritic phase, and SFB-dependent lung pathology requires the T helper 17 (Th17) responses. SFB-induced gut Th17 cells are preferentially recruited to lung over spleen due to robust expression in the lung of the Th17 chemoattractant, CCL20. Additionally, we found that in peripheral tissues, SFB selectively expand dual T cell receptor (TCR)-expressing Th17 cells recognizing both an SFB epitope and self-antigen, thus augmenting autoimmunity. This study reveals mechanisms for commensal-mediated gut-lung crosstalk and dual TCR-based autoimmunity.

Research paper thumbnail of The impact of age and gut microbiota on Th17 and Tfh cells in K/BxN autoimmune arthritis

Arthritis Research & Therapy

Background: Age is an important risk factor for rheumatoid arthritis (RA), which often develops i... more Background: Age is an important risk factor for rheumatoid arthritis (RA), which often develops in middle age. However, how age-associated changes in immunity impact RA is poorly understood. Gut microbiota are known to be involved in the pathogenesis of RA, but the effects of microbiota in older subjects remain mostly unknown. Methods: We used segmented filamentous bacteria (SFB), a gut commensal species with immunomodulatory effects, and K/BxN mice, a T cell receptor (TCR) transgenic model, to study the effect of age and microbiota on autoimmune arthritis. Comparing young and middle-aged K/BxN T cells of the same TCR specificity allows us to study T cells with an age focus eliminating a key variable: TCR repertoire alteration with age. In addition to joints, we also studied pathological changes in the lung, an important extra-articular RA manifestation. We used flow cytometry to evaluate T follicular helper (Tfh) and T helper 17 (Th17) cells, as they both contribute to autoantibody production, a key disease index in both RA and K/BxN arthritis. Results: Middle-aged K/BxN mice had aggravated arthritis and pathological changes in the lung compared to young mice. Middle-aged mice displayed a strong accumulation of Tfh but not Th17 cells, and had defective Th17 differentiation and low expression of interleukin-23, a critical cytokine for Th17 maintenance. Although a soaring Tfh cell population accompanied by robust germinal center B cell responses were found in middle-aged mice, there was decreased cycling of Tfh cells, and SFB only induced the non-Tfh cells to upregulate Bcl-6, the Tfh master transcription factor, in the young but not the middle-aged group. Finally, the accumulated Tfh cells in middle-aged mice had an effector phenotype (CD62L lo CD44 hi). Conclusion: Age-dependent Tfh cell accumulation may play a crucial role in the increased autoimmune disease phenotype in middle-age. SFB, a potent stimulus for inducing Tfh differentiation, fails to promote Tfh differentiation in middle-aged K/BxN mice, suggesting that most of the middle-aged Tfh cells with an effector phenotype are Tfh effector memory cells induced at an earlier age. Our results also indicate that exposure to immunomodulatory commensals may allow the young host to develop an overactive immune system reminiscent of that found in the middle-aged host.

Research paper thumbnail of Identifying species of symbiont bacteria from the human gut that, alone, can induce intestinal Th17 cells in mice

Proceedings of the National Academy of Sciences of the United States of America, Dec 13, 2016

Th17 cells accrue in the intestine in response to particular microbes. In rodents, segmented fila... more Th17 cells accrue in the intestine in response to particular microbes. In rodents, segmented filamentous bacteria (SFB) induce intestinal Th17 cells, but analogously functioning microbes in humans remain undefined. Here, we identified human symbiont bacterial species, in particular Bifidobacterium adolescentis, that could, alone, induce Th17 cells in the murine intestine. Similar to SFB, B. adolescentis was closely associated with the gut epithelium and engendered cognate Th17 cells without attendant inflammation. However, B. adolescentis elicited a transcriptional program clearly distinct from that of SFB, suggesting an alternative mechanism of promoting Th17 cell accumulation. Inoculation of mice with B. adolescentis exacerbated autoimmune arthritis in the K/BxN mouse model. Several off-the-shelf probiotic preparations that include Bifidobacterium strains also drove intestinal Th17 cell accumulation.

Research paper thumbnail of Synthetic Retinoid AM80 Ameliorates Lung and Arthritic Autoimmune Responses by Inhibiting T Follicular Helper and Th17 Cell Responses

Journal of immunology (Baltimore, Md. : 1950), Mar 1, 2017

Rheumatoid arthritis is an autoimmune disorder that affects the joints and other organs. Pulmonar... more Rheumatoid arthritis is an autoimmune disorder that affects the joints and other organs. Pulmonary complications contribute significantly to rheumatoid arthritis mortality. Retinoic acid and its synthetic compound AM80 play roles in immunoregulation but their effect on mucosal autoimmunity remains largely unknown. T follicular helper (Tfh) and Th17 cells are known to promote inflammation and autoantibody production. Using the K/BxN autoimmune arthritis model, we elucidate a novel mechanism whereby oral AM80 administration suppressed lung mucosa-associated Tfh and autoantibody responses by increasing the gut-homing α4β7 integrin expression on Tfh cells. This diverted Tfh cells from systemic (non-gut) inflamed sites such as the lung into the gut-associated lymphoid tissues, Peyer's patches, and thus reduced the systemic autoantibodies. AM80 also inhibited the lung Th17 response. AM80's effect in the lungs was readily applied to the joints as AM80 also inhibited Tfh and Th17 re...

Research paper thumbnail of Synthetic Retinoid AM80 Ameliorates Lung and Arthritic Autoimmune Responses by Inhibiting T Follicular Helper and Th17 Cell Responses

Journal of immunology (Baltimore, Md. : 1950), Mar 1, 2017

Rheumatoid arthritis is an autoimmune disorder that affects the joints and other organs. Pulmonar... more Rheumatoid arthritis is an autoimmune disorder that affects the joints and other organs. Pulmonary complications contribute significantly to rheumatoid arthritis mortality. Retinoic acid and its synthetic compound AM80 play roles in immunoregulation but their effect on mucosal autoimmunity remains largely unknown. T follicular helper (Tfh) and Th17 cells are known to promote inflammation and autoantibody production. Using the K/BxN autoimmune arthritis model, we elucidate a novel mechanism whereby oral AM80 administration suppressed lung mucosa-associated Tfh and autoantibody responses by increasing the gut-homing α4β7 integrin expression on Tfh cells. This diverted Tfh cells from systemic (non-gut) inflamed sites such as the lung into the gut-associated lymphoid tissues, Peyer's patches, and thus reduced the systemic autoantibodies. AM80 also inhibited the lung Th17 response. AM80's effect in the lungs was readily applied to the joints as AM80 also inhibited Tfh and Th17 re...

Research paper thumbnail of Macrophage as a mediator of immune response: Sustenance of immune homeostasis

Macrophage, 2015

Macrophages have evolved as a key player in our immune system. As macrophages remain groomed to c... more Macrophages have evolved as a key player in our immune system. As macrophages remain groomed to combat invasions by pathogens they also exhibit distinct polarized (M1/M2) states while adapting to the local environmental milieu. Detailed molecular mechanisms governing the prevalence of the usual steady state as well as altered (M1/M2) homeostasis programs under normal and pathogenic conditions remain to be deciphered. In this review, we have discussed the significance of immune homeostasis in macrophages and the involvement of Wnt-Frizzled signalling therein. Overall this review throws light upon some important questions related to the immune homeostasis scheme, answers to which will offer new insight in the field of immunology.

Research paper thumbnail of Designing of RNA aptamer against DNA binding domain of the glucocorticoid receptor: A response element-based in-silico approach

Journal of Biomolecular Structure and Dynamics

Research paper thumbnail of Wnt Signaling: Pathogen Incursion and Immune Defense

Research paper thumbnail of Segmented Filamentous Bacteria Provoke Lung Autoimmunity by Inducing Gut-Lung Axis Th17 Cells Expressing Dual TCRs

Cell host & microbe, Nov 8, 2017

Lung complications are a major cause of rheumatoid arthritis-related mortality. Involvement of gu... more Lung complications are a major cause of rheumatoid arthritis-related mortality. Involvement of gut microbiota in lung diseases by the gut-lung axis has been widely observed, but the underlying mechanism remains mostly unknown. Using an autoimmune arthritis model, we show that a constituent of the gut microbiota, segmented filamentous bacteria (SFB), distantly provoke lung pathology. SFB induce autoantibodies in lung during the pre-arthritic phase, and SFB-dependent lung pathology requires the T helper 17 (Th17) responses. SFB-induced gut Th17 cells are preferentially recruited to lung over spleen due to robust expression in the lung of the Th17 chemoattractant, CCL20. Additionally, we found that in peripheral tissues, SFB selectively expand dual T cell receptor (TCR)-expressing Th17 cells recognizing both an SFB epitope and self-antigen, thus augmenting autoimmunity. This study reveals mechanisms for commensal-mediated gut-lung crosstalk and dual TCR-based autoimmunity.

Research paper thumbnail of The impact of age and gut microbiota on Th17 and Tfh cells in K/BxN autoimmune arthritis

Arthritis Research & Therapy

Background: Age is an important risk factor for rheumatoid arthritis (RA), which often develops i... more Background: Age is an important risk factor for rheumatoid arthritis (RA), which often develops in middle age. However, how age-associated changes in immunity impact RA is poorly understood. Gut microbiota are known to be involved in the pathogenesis of RA, but the effects of microbiota in older subjects remain mostly unknown. Methods: We used segmented filamentous bacteria (SFB), a gut commensal species with immunomodulatory effects, and K/BxN mice, a T cell receptor (TCR) transgenic model, to study the effect of age and microbiota on autoimmune arthritis. Comparing young and middle-aged K/BxN T cells of the same TCR specificity allows us to study T cells with an age focus eliminating a key variable: TCR repertoire alteration with age. In addition to joints, we also studied pathological changes in the lung, an important extra-articular RA manifestation. We used flow cytometry to evaluate T follicular helper (Tfh) and T helper 17 (Th17) cells, as they both contribute to autoantibody production, a key disease index in both RA and K/BxN arthritis. Results: Middle-aged K/BxN mice had aggravated arthritis and pathological changes in the lung compared to young mice. Middle-aged mice displayed a strong accumulation of Tfh but not Th17 cells, and had defective Th17 differentiation and low expression of interleukin-23, a critical cytokine for Th17 maintenance. Although a soaring Tfh cell population accompanied by robust germinal center B cell responses were found in middle-aged mice, there was decreased cycling of Tfh cells, and SFB only induced the non-Tfh cells to upregulate Bcl-6, the Tfh master transcription factor, in the young but not the middle-aged group. Finally, the accumulated Tfh cells in middle-aged mice had an effector phenotype (CD62L lo CD44 hi). Conclusion: Age-dependent Tfh cell accumulation may play a crucial role in the increased autoimmune disease phenotype in middle-age. SFB, a potent stimulus for inducing Tfh differentiation, fails to promote Tfh differentiation in middle-aged K/BxN mice, suggesting that most of the middle-aged Tfh cells with an effector phenotype are Tfh effector memory cells induced at an earlier age. Our results also indicate that exposure to immunomodulatory commensals may allow the young host to develop an overactive immune system reminiscent of that found in the middle-aged host.

Research paper thumbnail of Identifying species of symbiont bacteria from the human gut that, alone, can induce intestinal Th17 cells in mice

Proceedings of the National Academy of Sciences of the United States of America, Dec 13, 2016

Th17 cells accrue in the intestine in response to particular microbes. In rodents, segmented fila... more Th17 cells accrue in the intestine in response to particular microbes. In rodents, segmented filamentous bacteria (SFB) induce intestinal Th17 cells, but analogously functioning microbes in humans remain undefined. Here, we identified human symbiont bacterial species, in particular Bifidobacterium adolescentis, that could, alone, induce Th17 cells in the murine intestine. Similar to SFB, B. adolescentis was closely associated with the gut epithelium and engendered cognate Th17 cells without attendant inflammation. However, B. adolescentis elicited a transcriptional program clearly distinct from that of SFB, suggesting an alternative mechanism of promoting Th17 cell accumulation. Inoculation of mice with B. adolescentis exacerbated autoimmune arthritis in the K/BxN mouse model. Several off-the-shelf probiotic preparations that include Bifidobacterium strains also drove intestinal Th17 cell accumulation.

Research paper thumbnail of Synthetic Retinoid AM80 Ameliorates Lung and Arthritic Autoimmune Responses by Inhibiting T Follicular Helper and Th17 Cell Responses

Journal of immunology (Baltimore, Md. : 1950), Mar 1, 2017

Rheumatoid arthritis is an autoimmune disorder that affects the joints and other organs. Pulmonar... more Rheumatoid arthritis is an autoimmune disorder that affects the joints and other organs. Pulmonary complications contribute significantly to rheumatoid arthritis mortality. Retinoic acid and its synthetic compound AM80 play roles in immunoregulation but their effect on mucosal autoimmunity remains largely unknown. T follicular helper (Tfh) and Th17 cells are known to promote inflammation and autoantibody production. Using the K/BxN autoimmune arthritis model, we elucidate a novel mechanism whereby oral AM80 administration suppressed lung mucosa-associated Tfh and autoantibody responses by increasing the gut-homing α4β7 integrin expression on Tfh cells. This diverted Tfh cells from systemic (non-gut) inflamed sites such as the lung into the gut-associated lymphoid tissues, Peyer's patches, and thus reduced the systemic autoantibodies. AM80 also inhibited the lung Th17 response. AM80's effect in the lungs was readily applied to the joints as AM80 also inhibited Tfh and Th17 re...

Research paper thumbnail of Synthetic Retinoid AM80 Ameliorates Lung and Arthritic Autoimmune Responses by Inhibiting T Follicular Helper and Th17 Cell Responses

Journal of immunology (Baltimore, Md. : 1950), Mar 1, 2017

Rheumatoid arthritis is an autoimmune disorder that affects the joints and other organs. Pulmonar... more Rheumatoid arthritis is an autoimmune disorder that affects the joints and other organs. Pulmonary complications contribute significantly to rheumatoid arthritis mortality. Retinoic acid and its synthetic compound AM80 play roles in immunoregulation but their effect on mucosal autoimmunity remains largely unknown. T follicular helper (Tfh) and Th17 cells are known to promote inflammation and autoantibody production. Using the K/BxN autoimmune arthritis model, we elucidate a novel mechanism whereby oral AM80 administration suppressed lung mucosa-associated Tfh and autoantibody responses by increasing the gut-homing α4β7 integrin expression on Tfh cells. This diverted Tfh cells from systemic (non-gut) inflamed sites such as the lung into the gut-associated lymphoid tissues, Peyer's patches, and thus reduced the systemic autoantibodies. AM80 also inhibited the lung Th17 response. AM80's effect in the lungs was readily applied to the joints as AM80 also inhibited Tfh and Th17 re...