Analysis of innate and adaptive immune responses.
Summary of Research:
The broad aim of the research efforts in my laboratory is to understand how systemic and mucosal immune responses are regulated under physiological conditions and under conditions of perturbed homeostasis. Using in vitro, ex vivo and in vivo approaches, and in collaboration with scientists within and outside the institute, we probe the role of cell-intrinsic and cell-extrinsic factors in modulating lymphocyte development and responses, in controlling cell fate determination choices, and in influencing memory/effector pool sizes. We also examine the contribution of innate and adaptive immune components and of microbial factors in determining the severity of experimental colitis.
Analysis of B cell responses: Our previous data indicate a) thatsignlaing through the TNF receptors CD27 or CD40 during B cell activation inhibits the generation of antibody secreting plasma cells while enhancing the generation of memory cells and b) that a subset of IgM+ “unswitched” memory B cells that expresses CD73 is generated through B cell-T cell interactions involving CD40. We are currently attempting to determine whether CD40-signaling contributes to the maintenance of the memory and plasma cell pools.
Analysis of T cell responses: We are examining the effect of fever-temperatures maintained during priming on T cell differentiation choices. We are also looking at the contribution of the non-canonical NF-kappaB pathway in the regulation/maintenance of immune homeostasis and the effect of dietary restriction on T cell development and function.
Role of host and microbial components in experimental colitis: We have found that conventional wildtype mice that differ in IgA responses show differential susceptibility to experimental colitis. We are trying to understand whether IgA affords protection through effects on barrier resilience and/or microbial loads and composition and/or bacterial exclusion.
Suman Gupta, Danish Umar, Atika Dhar
- Saini AS, Shenoy GN, Rath S, Bal V, George A (2014) Inducible nitric oxide synthase is a major intermediate in signaling pathways for plasma cell survival. Nat Immunol 15: 275-282
- Upadhyay M, Krishna Priya G, Ramesh P, Madhavi MB, Rath S, Ba; V, George A, Vaidya T (2014)CD40 signaling drives B lymphocytes into a memory-like state that is intermediate between naïve cells and plasma cells. J Cell Physiol 229: 1387-1396
- Rane S, Das R, Ranganathan V, Prabhu S, Das A, Mattoo H, Durdik JM, George A, Rath S, Bal V (2014) Peripheral residence of naïve CD4 T cells induces MHC class II-dependent alterations in phenotype and function. BMC Biology 12:106
- Basu S, Kaw S, D’Souza L, Vaidya T, Bal V, Rath S, George A (2016) Constitutive CD40-signaling calibrates differentiation outcomes in responding B cells via multiple molecular pathways. J Immunol 197: 761-770
- Balyan R, Gund R, Ebenezer C, Khalsa JK, Verghese DA, Krishnamurthy T, George A, Bal V, Rath S, Chaudhry A (2017) Modulation of naive CD8 T cell response features by ligand density, affinity, and continued signaling via internalized TCRs. J Immunol 198: 1823-1837
- Tanwar S, Dhar A, Varanasi V, Mukherjee T, Boppana R, Basak S, Bal V, George A, Rath S (2017).Mediation of transitional B cell maturation in the absence of functional Bruton's tyrosine kinase. Sci Rep 7:46029.
- D’Souza LD, Gupta SL, Bal VB, Rath S, George A (2017). CD73 expression identiﬁes a subset of IgM+antigen-experiencedcells with memory attributes that is T cell and CD40 signalling dependent. Immunology 152:602-612.
- Mukherjee T, Chatterjee B, Dhar A, Bais SS, Chawla M, Roy P, George A, Bal V, Rath S, Basak S (2017).A TNF-p100 pathway subverts noncanonical NF-κB signaling in inflamed secondary lymphoid organs. EMBO J 36:3501-3516.
- Das A, Ranganathan V, Umar D, Thukral S, George A, Rath S, Bal V (2017). Effector/memory CD4 T cells making either Th1 or Th2 cytokines commonly co-express T-bet and GATA-3. PLoS One.12(10):e0185932.
- Balyan R, Gund R, Chawla AS, Khare S, PradhanS, Rane S, Galande S, Durdik J, George A, Bal V, Rath S. (2018). Correlation of Cell-Surface CD8 Levels with Function, Phenotype and Transcriptome of Naive CD8 T Cells. Immunology doi: 10.1111/imm.13036.
- Chawla AS, Kanodia P, Mukherjee A, Jain V, Kaur G, Coshic P, Chatterjee K, Wadhwa N, Natchu UCM, Sopory S, Bhatnager S, Majumder PP, George A, Bal V, Rath S, Prabhu SB (2018). Cell-intrinsic regulation of peripheral memory-phenotype T cell frequencies. PLoS One. 13(12):e0200227.