Anil K. Chauhan, Ph.D.

Anil K. Chauhan, Ph.D.Anil K. Chauhan, Ph.D.
Associate Professor
Division of Adult and Pediatric Rheumatology

Research Interest

The current paradigm propose that the CD4+ T-cells do not express low affinity FcgRIIIa1.  We observed that the Jurkat cells treated with immune complexes (ICs) in the presence of sublytic amounts of late complement proteins (C5b-9) triggered phosphorylation of T cell receptor (TCR) signaling proteins and labeled ICs bound to these cells2. Subsequently, we identified this IC binding protein as FcgRIIIa receptor, which preferentially bind to the ICs3. Our work have now shown that the FcgRIIIa signaling is a new immune checkpoint signal for human CD4+ T-cells that result in the generation of proinflammatory effector CD4+ T- helper cells. FcgRIIIa cosignaling differentiates naïve human CD4+ T-cells into Th1, Th17 and Tfh populations. This is a paradigm shift in our current understanding of CD4+ T-cell biology. FcgRIIIa signal successfully replaces CD28 requirement and rescue these cells from becoming anergic upon TCR activation.  Specific blocking of FcgRIIIa signal on CD4+ T-cells provide a new therapeutic target for autoimmune diseases and cancer.  Understanding the role of FcgRIIIa signaling in CD4+ T-cell responses will advance the development of the T-cell based therapies.  Low affinities Fc-receptors (FcRs) are critical participants in the antigen processing/proteasome assembly and intracellular trafficking. Signaling from FcRs trigger cytokine production by monocyte, B-cells, and plasmacytoid dendritic cells (pDCs), which trigger autoimmune response. Despite some earlier studies supporting the role of low affinity FcRs in the adaptive immune response, literature over past two decades has ignored the role of FcgRIIIa signal in CD4+ T-cell function. We have now shown that in systemic lupus erythematosus (SLE)- CD4+ T-cells, FcgRIIIa signal up regulates the expression of nucleic acid sensing toll-like (NA-TLRs) receptors4,5. TLR9 one of three NA-TLRs by driving production of interferons (IFNs) from pDCs contribute to the SLE pathogenesis. Our recent work have also shown that TLR9 accumulated as uncleaved full length 120-kDa protein at the cell surface in CD4+ T-cells, where it recognized CpG ODN 2006 and localized with FcgRIIIa within the CD3 complex. These findings establish a previously unknown pathway that will provide new therapeutic targets.  TLR9 on the cell surface recognizes modified self-DNA and not the viral-DNA, which is recognized in the acidic endosomes. These findings from my laboratory describe a new novel mechanism for the development of autoimmune pathology. Further understanding of these pathways will assist in developing NA-TLR agonist based therapies for autoimmune disorders.  My group has also shown that both MyD88 and HMGB1 associate with FcgRIIIa protein on the cell surface4,5. These two proteins are required for TLR signaling and DNA sensing. These proteins form a signaling complex similar to myddosome observed in innate cells. RNA-seq data from FcgRIIIa cosignaling, when compared to CD28 show upregulation of IL-27, IFNl2, IFNl3, IFNl, IFNw1, and IFNb1. This was accompanied with increase in NF-kB transcripts and upregulation of IFN inducible genes i.e. IFITM1, IFITM10, IFI6, IFIH1 and IFITM5. Proinflammatory cytokines IL-1a, IL-1b, IL-2, IL-17A, IL-22, IL-23, IL-31RA, and IL-34 were also upregulated. Upregulation of IFIH1 suggests an ongoing nucleic acid sensing via RIG1 pathway. FcgRIIIa signal induces expression of gene transcripts from pathways, such as cellular response to DNA damage and RNA-binding. FcgRIIIa cosignal also up regulated 204 genes from ERK signaling pathway. FcgRIIIa cosignal differentially expressed the small non-coding RNA both miRNAs, lincRNAs and 1139 genes from extracellular exosomes. This raises the possibility by loading exosomes with regulatory lincRNAs, the FcgRIIIa signal exercises a role in intercellular regulation. Two RNAs, HOTTIP and HOTAIR, which are known biomarkers in cancer and regulate T-cell responses, are also upregulated by FcgRIIIa cosignaling.  Focus of my laboratory is to explore the role of FcgRIIIa and NA-TLRs and their synergistic signaling in CD4+ T-cell responses.  To further examine the innate immune sensors in CD4+ T-cells during autoimmunity.


  1. Bruhns, P. & Jonsson, F. Mouse and human FcR effector functions. Immunol Rev 268, 25-51 (2015),
  2. Chauhan, A.K. & Moore, T.L. T cell activation by terminal complex of complement and immune complexes. J Biol Chem 286, 38627-38637 (2011).PMC3207410.
  3. Chauhan, A.K., et al. Induced Expression of FcgammaRIIIa (CD16a) on CD4+ T Cells Triggers Generation of IFN-gammahigh Subset. J Biol Chem 290, 5127-5140 (2015).PMC4335247.
  4. Chauhan, A.K. FcgammaRIIIa Signaling Modulates Endosomal TLR Responses in Human CD4+ T Cells. J Immunol (2017),
  5. Chauhan, A.K., et al. FcgammaRIIIa-Syk Co-signal Modulates CD4+ T-cell Response and Up-regulates Toll-like Receptor (TLR) Expression. J Biol Chem 291, 1368-1386 (2016).PMC4714221.

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